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Showing papers on "Area postrema published in 1992"


Journal ArticleDOI
TL;DR: Findings support the existence of multiple pathways by which peripheral chemoreceptor inputs may influence central respiratory neurons in the rat, and suggest carotid body afferents may also interact more directly with respiratory- or cardiovascular-related neurons in other regions such as the ventrolateral medulla.

389 citations


Journal ArticleDOI
TL;DR: Brain Ang II receptor subtypes were differentiated into AT‐1 (type I) and AT‐2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes.
Abstract: Angiotensin II (Ang II) exerts a number of central actions on fluid and electrolyte homeostasis, autonomic activity, and neuroendocrine regulation. In order to evaluate likely sites where these actions are mediated, Ang II receptor binding was localized in rat brain by in vitro autoradiography with the aid of the antagonist analogue l25I-[Sar1, Ile8]Ang II. Two subtypes of Ang II receptor have been identified using recently developed peptide and nonpeptide antagonists. In the periphery, the receptor subtypes differ in distribution, second messenger coupling, and function. Brain Ang II receptor subtypes were therefore differentiated into AT-1 (type I) and AT-2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes. AT-1 binding was determined to be that inhibited by Dup 753 (10 μM) and AT-2 binding to be that inhibited by PD 123177 (10 μM). The reducing agent dithiothreitol (DTT) decreased binding to AT-1 receptors and enhanced binding to AT-2 receptors. Many brain structures, such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, which are known to be related to the central actions of Ang II, contain exclusively AT-1 Ang II receptors. By contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus and subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 Ang II receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of analogues of angiotensin and antagonists. The pharmacological specificity obtained in rat superior colliculus and the nucleus of the solitary tract agreed well with published data on AT-1 and AT-2 receptors, respectively. There was a high degree of correlation between the distribution of Ang II binding sites with published data on Ang II-immunoreactive fields and on the sites of Ang II-responsive neurons. The present study also reveals pharmacological heterogeneity of brain Ang II receptors. The subtype-specific receptor mapping described here is relevant to understanding the role of angiotensin peptides in the central nervous system and newly discovered central actions of nonpeptide Ang II receptor antagonists.

318 citations


Journal ArticleDOI
01 Apr 1992-Synapse
TL;DR: Assays with membranes from the posterior (mainly entorhinal) cortex confirmed that the pharmacolgical properties and regional distribution of [125I]iodo‐zacopride‐specific binding sites were identical with those of 5‐HT3 sites labelled by the reference radioligand [3H].
Abstract: Substitution of the chlorine atom by a radio-iodine in position 5 in the zacopride molecule yielded [125I]iodo-zacopride that bound with high affinity (Kd = 4.3 nM) to 5-HT3 receptors in the rat central nervous system. Assays with membranes from the posterior (mainly entorhinal) cortex confirmed that the pharmacological properties and regional distribution of [125I]iodo-zacopride-specific binding sites were identical with those of 5-HT3 sites labelled by the reference radioligand [3H]zacopride. Autoradiographic investigations for the visualization and quantification of 5-HT3 receptors yielded similar results with both radioligands, but autoradiograms could be obtained after only 1-3 days of exposure of sections labelled with [125I]iodo-zacopride, instead of 4-6 months using [3H]zacopride. The highest density of 5-HT3 sites was found in the nucleus tractus solitarius followed by, in decreasing order, the dorsal motor nucleus of the vagus nerve, the superficial layers of the dorsal horn in the spinal cord, the nucleus of the spinal tract of the trigeminal nerve, and the area postrema. Significant labelling of 5-HT3 receptors was also observed in limbic areas (amygdala, hippocampus, frontal and entorhinal cortex), and to a much lower extent in the dorsal raphe nucleus, striatum, and substantia nigra. These multiple locations further support the idea that 5-HT3 receptors are probably involved in several 5-HT-mediated functions in the central nervous system.

170 citations


Journal ArticleDOI
TL;DR: The results suggest that blood-borne angiotensin II at physiological levels causes angioten receptive neurons in the subfornical organ and OVLT to express Fos, and activation of baroreceptor pathways may also induce Fos expression at several other sites.

167 citations


Journal ArticleDOI
TL;DR: It is inferred that treatment with 5‐HT1B/d agonists may be useful for the alleviation of pain in other headache conditions associated with meningeal irritation and that 5‐ HT1D receptor‐mediated blockade of neurotransmission contributes significantly to the analgesic effects of these drugs in headache.
Abstract: 1. The effects of intravenously administered 5-HT1B receptor agonists were examined on c-fos like immunoreactivity, an indicator of neuronal activation, within the brain stem. C-fos was induced by injecting an algesic, vasoconstrictor substance (0.3 ml of autologous blood) or a pro-inflammatory molecule, carrageenin (1 mg in 0.1 ml saline) into the cisterna magna of pentobarbitone-anaesthetized Sprague-Dawley rats and was visualized in serial sections (50 micrometers) by use of a polyclonal antiserum. 2. As previously reported, the injection of blood caused significant labelling within laminae I, IIo of the trigeminal nucleus caudalis, a major nociceptive brain stem nucleus, as well as within nucleus of the solitary tract and area postrema. A similar pattern of expression with fewer cells per section was detected after carrageenin instillation. The number of expressing cells was reduced by 54% in trigeminal nucleus caudalis but not within the nucleus of the solitary tract or area postrema when blood was injected in adult rats neonatal capsaicin treatment. 3. Pretreatment with 5-HT1 agonists with some selectivity for the 5-HT1B receptor, CP-93,129 (460 nmol kg-1 x 2, i.v.), sumatriptan (720 nmol kg-1 x 2, i.v.) or dihydroergotamine (86 nmol kg-1 x 2, i.v.) reduced positive cells by 39%, 31%, and 33% respectively in trigeminal nucleus caudalis but not in nucleus of the solitary tract or area postrema after blood instillation. Pretreatment with the analgesic morphine (15 mumol kg-1, s.c.) also decreased the number of positive cells by 63% in trigeminal nucleus caudalis. 4. CP-93,129 (460 nmol kg-1 x 2, i.v.) reduced the number of c-fos labelled cells by 47% within lamina I, IIo after carrageenin instillation. 5. Drug-induced blockade appeared to be tissue-dependent. Pretreatment with sumatriptan (720 nmol kg-1 x 2, i.v.) did not block c-fos expression in trigeminal nucleus caudalis following formalin application to the nasal mucosa.6. Drug-induced blockade may be mediated by an action on primary afferent (trigeminovascular) fibres in as much as CP-93,129 (460 nmol kg-' x 2, i.v.) did not reduce the number of expressing cells within the trigeminal nucleus caudalis following blood instillation in rats treated as neonates with capsaicin.7. We infer from these results that the analgesic actions of agonists at 5-HTB receptors (the receptor subtype analogous to 5-HTID in man) need not depend upon the presence of vasodilatation and, that 5-HTID receptor-mediated blockade of neurotransmission contributes significantly to the analgesic effects of these drugs in headache.8. Based on the demonstrated effects of 5-HTB/D agonists against the actions of two chemicallyunrelated meningeal stimulants, we suggest that treatment with 5-HTID agonists may be useful for the alleviation of pain in other headache conditions associated with meningeal irritation. Bacterial, viral(including AIDS meningovascular inflammation) and other forms of chemical meningitis merit further investigation.

138 citations


Journal ArticleDOI
TL;DR: An abbreviated atlas of the rat subpostremal NTS consisting of a series of transverse, sagittal, and horizontal plates is provided and photomicrographs are provided for the serial sections generated from each reference plane.

137 citations


Journal ArticleDOI
TL;DR: It is concluded that blood in the subarachnoid space is an effective stimulus for activating c-fos expression within subpopulations of brainstem neurons.

134 citations


Journal ArticleDOI
TL;DR: The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl and results suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance.
Abstract: The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.

128 citations


Journal ArticleDOI
TL;DR: Using dual fluorescent immunocytochemistry for Fos‐like protein and tyrosine hydroxylase (TH), catecholaminergic cells in the A2 region of the NTS and the A1 regions of the lateral reticular area were shown to be activated.
Abstract: Ninety min after intraperitoneal (ip) injection of Cholecystokinin (CCK, 50 μg/kg body wt) Fos-like protein was expressed in cells throughout the nucleus of the tractus solitarii (NTS) and area postrema, and also in scattered cells in the lateral reticular area of the brainstem. Using dual fluorescent immunocytochemistry for Fos-like protein and tyrosine hydroxylase (TH), catecholaminergic cells in the A2 region of the NTS and the A1 region of the lateral reticular area were shown to be activated.

106 citations


Journal ArticleDOI
TL;DR: Results define central pathways involved in mediating the baroreceptor reflex as well as moderate amounts of label were present in the supraoptic nucleus and periventricular hypothalamus bilaterally in control animals.

104 citations


Journal ArticleDOI
TL;DR: Vagal sensory fibres mediate CCK‐induced c‐fos in brain stem neurons, based on the findings that perivagal capsaicin pre‐treatment in seven out of eight cases reduced or ablated c-fos expression in these regions.
Abstract: Exogenous cholecystokinin (CCK) activates brain stem neurons in the area postrema and nucleus of the tractus solitarius, primarily in regions where vagal afferent fibres terminate. The present experiments show that vagal sensory fibres mediate CCK-induced c-fos in brain stem neurons, based on the findings that perivagal capsaicin pre-treatment in seven out of eight cases reduced or ablated c-fos expression in these regions.

Journal ArticleDOI
TL;DR: Findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin, and provide strong evidence that the failure to acquire conditioned taste aversions after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.

Journal ArticleDOI
TL;DR: It is demonstrated that CaBP28k‐containing cells form a major part of the solitary and trigeminal projection systems, including subregions that are involved in visceroception and/or nociception processing.
Abstract: This study concerns the involvement of calbindin-D28K (CaBP28k)-containing neurons in the efferent projections of both the trigeminal nucleus caudalis and the dorsal vagal complex (nucleus of the solitary tract and area postrema) in rats. Recent evidence has shown that these projections are particularly important for the processing of visceroception and/or nociception at central levels. The trigeminal nucleus caudalis has dense projections to both the nucleus of the solitary tract and the parabrachial area; the dorsal vagal complex is intimately connected to the parabrachial area. CaBP28k is a calcium-binding protein the function of which could be a determining factor in controlling the excitability of cells by acting on intrinsic calcium metabolism. CaBP28k content of projections was ascertained using a double labelling approach that combined the retrograde transport of a protein - gold complex to identify projection cells and immunocytochemistry to identify CaBP28k-positive cells. The trigeminal nucleus caudalis is rich in both CaBP28k-immunoreactive cells and cells projecting to the parabrachial area or the nucleus of the solitary tract. Cells containing both the protein and the retrograde tracer, however, were mostly restricted to the superficial layers (laminae I and outer II) and to their rostral extensions, the dorsal paramarginal and paratrigeminal nuclei. These trigeminal subdivisions are targets for nociceptive, visceroceptive and thermal inputs of peripheral origins. The dorsal vagal complex is rich in CaBP28k. Dense populations of immunoreactive cells are observed in the ventrolateral part of the area postrema and all of the three main subdivisions of the nucleus of the solitary tract (rostral gustatory, ventrolateral respiratory and medial cardiovascular subregions). The subnucleus commissuralis, subnucleus centralis and dorsal subnuclei are particularly densely stained. The subnucleus centralis, which is involved in regulating food and water intake, does not project to the parabrachial area. The area postrema, subnucleus commissuralis and dorsal subnuclei, which are implicated in cardiovascular and/or ingestive behaviours, have dense projections to the parabrachial area, many of which contain CaBP28k. The present results demonstrate that CaBP28k-containing cells form a major part of the solitary and trigeminal projection systems, including subregions that are involved in visceroception and/or nociception processing. The location of solitary nucleus projection cells overlaps those of some neuropeptidergic projecting populations, suggesting colocalization. Consequently, certain neuropeptidergic actions may be CaBP28k-dependent.

Journal ArticleDOI
TL;DR: In hemorrhaged rats, a higher concentration of Fos-stained neurons was present in the lamina terminalis, particularly the subfornical organ and organum vasculosum of the lAMA, and in the supraoptic and paraventricular nuclei of the hypothalamus, and it is hypothesize that those neurons are involved in mediating the physiological responses to hemorrhage.

Journal ArticleDOI
01 Jan 1992-Oncology
TL;DR: Clinical data showing that a single dose of ondansetron prevents acute emesis suggest that it is important to block the initiation of the emetic reflex, which may prevent the recruitment of central mechanisms involving 5-HT3 receptors.
Abstract: Ondansetron, a potent and highly selective 5-HT3 receptor antagonist, prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT3 receptors on vagal afferent neurons that innervate the gastrointestinal tract and 5-HT3 receptors in the central vomiting system Evidence suggests that chemotherapy induces the release of 5-HT from enterochromaffin cells in the small intestine This stimulates vagal afferent nerves via 5-HT3 receptors Information is then relayed, via the vagus nerve, to the central vomiting system 5-HT3 receptors are also found in the hind-brain vomiting system including the area postrema (the site of the chemoreceptor trigger zone for emesis) Therefore, following chemotherapy, 5-HT activates 5-HT3 receptors at 2 sites to induce emesis Clinical data showing that a single dose of ondansetron prevents acute emesis suggest that it is important to block the initiation of the emetic reflex This may prevent the recruitment of central mechanisms involving 5-HT3 receptors

Journal ArticleDOI
TL;DR: It is suggested that neurons in the mNST mediate the information from both the abdominal vagal afferents and the area postrema and drive the pattern generator for retching and vomiting, which is assumed to be located in the Bötzinger complex.

Journal ArticleDOI
TL;DR: Several novel brainstem regions, including the dorsomedial cell column of the inferior olive and the periaqueductal gray, as well as more traditional brainstem nuclei including vestibular and oculomotor related nuclei, respond to otolith activation during a sustained centripetal acceleration.
Abstract: To identify rat brainstem nuclei involved in the initial, short-term response to a change in gravito-inertial force, adult Long-Evans rats were rotated in the horizontal plane for 90 min in complete darkness after they were eccentrically positioned off the axis of rotation (off- axis) causing a centripetal acceleration of 2 g. Neural activation was defined by the brainstem distribution of the c-fos primary response gene protein, Fos, using immunohistochemistry. The Fos labeling in off- axis animals was compared with that of control animals who were rotated on the axis of rotation (on-axis) with no centripetal acceleration, or who were restrained but not rotated. In the off-axis animals there was a significant labeling of neurons: in the inferior, medial, and y-group subnuclei of the vestibular complex; in subnuclei of the inferior olive, especially the dorsomedial cell column; in midbrain nuclei, including the interstitial nucleus of Cajal, nucleus of Darkschewitsch, Edinger-Westphal nucleus, and dorsolateral periaqueductal gray; in autonomic centers including the solitary nucleus, area postrema, and locus coeruleus; and in reticular nuclei including the lateral reticular nucleus and the lateral parabrachial nucleus. Also, there was greater Fos expression in the dorsomedial cell column, the principal inferior olive subnuclei, inferior vestibular nucleus, the dorsolateral central gray, and the locus coeruleus in animals who had their heads restrained compared to animals whose heads were not restrained. As one control, the vestibular neuroepithelium was destroyed by injecting sodium arsanilate into the middle ear, bilaterally. This resulted in a complete lack of Fos labeling in the vestibular nuclei and the inferior olive, and a significant reduction in labeling in other nuclei in the off-axis condition, indicating that these nuclei have a significant labyrinth-sensitive component to their Fos labeling. The data indicate that several novel brainstem regions, including the dorsomedial cell column of the inferior olive and the periaqueductal gray, as well as more traditional brainstem nuclei including vestibular and oculomotor related nuclei, respond to otolith activation during a sustained centripetal acceleration.

Journal ArticleDOI
TL;DR: The results indicate that baroreceptor activation induces Fos expression in circumscribed medullary regions which have previously been shown to receive excitatoryBaroreceptor inputs.

Journal Article
TL;DR: In this paper, the locations of serotonin-3 (5-HT3) receptors involved in initiating vomiting were assessed by cutting visceral afferents or lesioning the area postrema.
Abstract: The locations of serotonin-3 (5-HT3) receptors involved in initiating vomiting (emesis) were assessed by cutting visceral afferents or lesioning the area postrema. The 5-HT3 receptor agonists phenylbiguanide (PBG) and 2-methyl-5-HT were shown to induce vomiting and related prodromal signs (e.g., licking, swallowing) in nonoperated cats. Two-methyl-5-HT, but not PBG, also usually produced defecation and sometimes urination. Most studies were conducted using PBG, which induced vomiting in 40/49 (82%) cats at doses of 8.0 mg/kg i.p. or less (thresholds ranged from 2-8 mg/kg, median 5 mg/kg). Latencies to the first episode ranged from 4 to 21 min (median 7.5 min). PBG-induced vomiting was blocked by the 5-HT3 receptor antagonist MDL 72222. Lesions of the area postrema had no apparent effect on vomiting induced by PBG or by electrical stimulation of abdominal vagal afferents. In contrast, the threshold of PBG-induced vomiting was increased by supradiaphragmatic vagotomy and greatly increased by splanchnic nerve section. Thus, abdominal visceral afferents, but not the area postrema, play an important role in mediating vomiting induced by i.p. injection of the 5-HT3 receptor agonist PBG. The mechanisms by which vomiting is induced by PBG as compared to the cancer chemotherapeutic drug cisplatin are discussed.

Journal ArticleDOI
01 Mar 1992-Synapse
TL;DR: Serotonin (5HT) binding sites in autonomic portions of the dorsomedial medulla oblongata of the rat were localized using autoradiographic techniques with radioactive ligands that express high affinity for the 5HT1 (3H‐5HT), 5 HT1A ( 3H‐8OH‐DPAT), or 5HT 1B (125I‐CYP with isoproterenol) receptor subtypes.
Abstract: Serotonin (5HT) binding sites in autonomic portions of the dorsomedial medulla oblongata of the rat were localized using autoradiographic techniques with radioactive ligands that express high affinity for the 5HT1 (3H-5HT), 5HT1A (3H-8OH-DPAT), or 5HT1B (125I-CYP with isoproterenol) receptor subtypes. 5HT1A sites were densely distributed in the nucleus tractus solitarius (NTS), with the highest densities localized to the interstitial subnucleus and the central subnucleus. 5HT1B sites were also found in the NTS, with the highest densities localized to the substantia gelatinosa subnucleus. The dorsal motor nucleus of the vagus nerve and nucleus ambiguus exhibited low densities of 5HT1B sites. However, the nucleus intercalatus, a cerebellar relay nucleus that also contains dendrites of vagal parasympathetic preganglionic neurons and receives autonomic forebrain afferent input, showed very dense 5HT1B sites. The promontorium, paratrigeminal islands, and the dorsomedial portion of the trigeminal nucleus (DM5), which are areas of viscerosomatic integration, exhibited high densities of both 5HT1A and 5HT1B sites. The area postrema contained low levels of both 5HT1A and 5HT1B sites. Visceral deafferentation via cervical vagotomy or nodose ganglionectomy caused a significant decrease in 5HT1A sites in the interstitial subnucleus of the NTS ipsilateral to the lesion. No changes were seen in 5HT1B sites. These studies suggest that 5HT1A and 5HT1B sites are involved in the processing of visceral sensory information in the NTS and associated areas. Based upon viscerotopic organization of the NTS, 5HT1A sites appear preferentially distributed in portions of the NTS that are associated with the coordination of swallowing, respiration, and cardiovascular function, while 5HT1B sites appear preferentially distributed in areas of the NTS associated with gastrointestinal, hepatic, pancreatic, and cardiovascular function. However, since these associations were not absolute and there was a great deal of overlap between the two sites, speculation regarding their specific functions in autonomic control must await pharmacological examination.

Journal ArticleDOI
TL;DR: Evidence suggests ANG II acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.
Abstract: Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.

Journal ArticleDOI
TL;DR: The results implicate mu receptors (possibly mu 1) in the induction of emesis by loperamide and provide some support for activation of opiate receptors also having anti-emetic effects, as suggested in previous studies.

Journal ArticleDOI
TL;DR: Findings provide further evidence for the widespread, topographic distribution of CCK receptors and indicate that [125l]d‐Tyr25(Nle28,31)‐CCK 25–33S is very suitable for autoradiographic investigations because of its low non‐specific binding.
Abstract: The distribution of receptors for the sulphated octapeptide cholecystokinin 26 - 33 (CCK - 8S) in rat brain was investigated by radioligand binding in conjunction with autoradiography using the novel iodinable, non-oxidizable, amino- and thiolendopeptidase-resistant CCK analogue, d-Tyr25(Nle28,31)-CCK 25 - 33S. Labelling of the peptide was achieved by synthesis utilizing Na125I and Chloramine-T. [125I]d-Tyr25(Nle28,31)-CCK 25 - 33S (100 pM) bound rapidly and reversibly to a single population of sites on slide-mounted coronal sections of rat forebrain with a dissociation constant of 34 pM. Specific binding was fully inhibited by CCK-8S, CCK-8, CCK-4, L-365,260 and L-364,718, with inhibition constants 2.7, 9.8, 35, 7.0 and 130 nM, respectively. These inhibition data may indicate that the [125I] ligand binds preferentially to a CCKB subtype of receptor, but may also reflect the relative paucity of CCKA receptors in the rat forebrain. Optimum conditions for autoradiography combined the preincubation of brain sections in unlabelled 10 pM d-Tyr25(Nle28,31)-CCK 25 - 33S with a 60-min wash after incubation with the [125I] ligand. Analyses of the autoradiograms obtained from the use of coronal and horizontal brain sections were aided by the high levels of specific binding (80 - 90%), and revealed that CCK receptors were topographically distributed through the neuroaxis. High densities of receptor-associated silver grains were found in the olfactory bulb (internal plexiform layer), neocortex (layer III), nucleus accumbens, parasubiculum, subbrachial nucleus, parabigeminal nucleus, dorsal vagal complex, area postrema and the A2 region. Moderate labelling was observed in many telencephalic and diencephalic nuclei. The majority of these receptors were of the CCKB subtype, as shown by the use of subtype-selective antagonists, although CCKA receptors were present in moderate to high densities in the A2 area, area postrema and nucleus tractus solitarii, and at low density in the interpeduncular nucleus and central amygdala. These findings provide further evidence for the widespread, topographic distribution of CCK receptors and indicate that [125I]d-Tyr25(Nle28,31)-CCK 25 - 33S is very suitable for autoradiographic investigations because of its low non-specific binding.

Journal ArticleDOI
TL;DR: Glycine immunolabelling was found preferentially in post-synaptic elements, suggesting that the glycine-containing cells lack locally ramifying axon collaterals, and that they mainly project outside the area postrema.
Abstract: The localization of five neuroactive amino acids in the rat area postrema was studied by postembedding immunocytochemistry in semithin and ultrathin sections. Antisera to GABA, glycine, glutamate and aspartate produced labelling of cells that were identified as neurons in the electron microscope. GABA-like and glycine-like immunoreactivities occurred in about 20% and 60% of the neurons, respectively, and a minor proportion of the cells displayed both immunoreactivities, suggesting a cellular colocalization of GABA and glycine. Immunoreactivities for glutamate and aspartate were found in a large majority of the neurons, including most of the cells that were positive for GABA and/or glycine. Taurine immunoreactivity was highly concentrated in a few small cells with ultrastructural features typical of microglial cells, and in processes that were probably derived from these. Taurine also appeared to be abundant in cells confined to the perivascular space. The electron microscopic, immunogold analysis of the neuropil revealed numerous nerve terminals that were enriched in GABA or glutamate immunoreactivity, compatible with a transmitter role of these amino acids. Glycine immunolabelling was found preferentially in postsynaptic elements, suggesting that the glycine-containing cells lack locally ramifying axon collaterals, and that they mainly project outside the area postrema. Aspartate immunolabelling was also generally low in axon terminals. This is similar to the situation in several other brain areas and could indicate that the latter amino acid primarily serves metabolic functions in the area postrema.


Journal ArticleDOI
TL;DR: The results suggest that neuropeptide Y, angiotensin II and galanin may serve as neurochemical messengers in pathways from the medulla to the parabrachial complex and suggest that the information relayed by these neurons is related to autonomic activity.

Journal ArticleDOI
TL;DR: The data suggest that MT receptor expression is differentially regulated during development and that permanent alterations in MT levels do not affect rat MT receptor status.
Abstract: To gain some understanding of the factors regulating high affinity melatonin (MT) receptors in the rat, we conducted a series of studies using quantitative autoradiography of [2-125I]iodo-MT binding in vitro with validated assay conditions. MT receptor status and the relative protein content of the autoradiographic sections were assessed in the anterior pituitary gland, the area postrema, the caudal (tail) artery (CA), the anterior cerebral artery (ACA), and the suprachiasmatic nuclei (SCN) of 9-, 96-, and 306-day-old Wistar rats. When age-associated changes in protein content were taken into account, MT receptor expression in the area postrema and the SCN remained relatively constant between 9-306 days of age. On the contrary, a dramatic loss of MT receptors was observed in the arteries of 306-day-old rats (98% and 89% loss compared to the 9-day-old rats in the ACA and CA, respectively). In the anterior pituitary gland, MT receptors were expressed only in the 9-day-old rats. The above changes reflected major changes in binding capacity and minor changes in binding affinity. Neither removal of endogenous circulating MT (acute light exposure for 24 h, pinealectomy, or superior cervical ganglionectomy) nor MT injections (1 mg/kg for 10 days 6 h after lights on) affected MT receptor status in the ACA, CA, area postrema, or SCN. Our data suggest that MT receptor expression is differentially regulated during development and that permanent alterations in MT levels do not affect rat MT receptor status.

Journal ArticleDOI
TL;DR: The localization of the expression of c-fos and NGFI-A mRNAs represents a useful neuroanatomical technique for detecting the cell bodies of neurones that are activated by cardiovascular nerve afferents and should allow the further characterization of the neurochemical identity of these neurones.

Journal ArticleDOI
TL;DR: The results of these studies recognize vitamin D-soltriol as a steroid hormone with a wide scope of hormone-specific target cells, similar to estrogen, androgen, and adrenal steroids, and which are topographically distinct and characteristic for its functions as the steroid hormone of sunlight.
Abstract: Autoradiograms were prepared from midbrains and hindbrains of male and female Siberian hamsters (Phodopus sungorus), kept under short-day or long-day illumination, after injection of tritium-labeled 1,25-dihydroxycholecalciferol (vitamin D, soltriol). Concentration and retention of radioactivity was noted in nuclei of certain neurons, glial cells, and ependymal cells, and in choroid epithelium. Labeled neurons of varying intensity were found throughout the brainstem in distinct populations at characteristic topographical sites, which include cranial nerve motor nuclei, the nucleus (n.) reticularis tegmenti pontis, the caudoventral region of the n. raphe dorsalis, the n. trapezoides, the n. vestibularis lateralis and n. vestibularis superior, neurons in the various nuclei of the sensory trigeminus, accessory optic nuclei, scattered neurons in nuclei of the reticular formation, the n. ambiguus, certain cells in the area postrema, and many others. Glial cells with nuclear labeling, probably microglia, were scattered predominantly in or near myelinated nerve fascicles. The choroid epithelium showed strong nuclear labeling throughout the ventricle. Nuclear labeling of ependyma was variable and weak, mainly at ventral and lateral extensions (recesses) of the ventricle. The extensive presence of nuclear binding in select neural structures indicates that vitamin D exerts specific genomic effects on cell populations that are known to be involved in the regulation of motor, sensory, autonomic, neuroendocrine, metabolic, and immune functions. The results of these studies, in conjunction with those from other brain and peripheral tissues, recognize vitamin D-soltriol as a steroid hormone with a wide scope of hormone-specific target cells, similar to estrogen, androgen, and adrenal steroids, and which are topographically distinct and characteristic for its functions as the steroid hormone of sunlight.

Journal ArticleDOI
TL;DR: The results suggest that the specific [125I]BK binding sites in the guinea pig medulla are of the bradykinin B2 receptor type.