Effects of centrally administered neuropeptide Y (NPY) and NPY13–36 on the brain monoaminergic systems of the rat
TL;DR: The most consistent finding was a dose-related increase of both DA and DOPAC levels after treatment with NPY, which was reproduced by NPY13–36 in cortical tissue, whereas, in the sub-cortical regions, NPY 13–36 only reproduced the effects of NPY on the DOPac levels.
Abstract: The effects of centrally administered NPY on the brain monoamine systems were investigated in the rat. Neuropeptide Y (0.2-5.0 nmol), its C-terminal 13-36 amino acid (a.a.) fragment, NPY13-36 (0.4-10.0 nmol), or saline were injected into the right lateral cerebral ventricle of unrestrained rats. After 1 h the animals were decapitated, and the brains were taken out. Two cortical regions ('frontal' and 'parietal'), the striatum, the hypothalamus, and the brain stem were dissected out. The tissue contents of noradrenaline (NA), dopamine (DA) and serotonin (5-HT), as well as of their major metabolites, 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indole acetic acid (5-HIAA) were measured. The most consistent finding was a dose-related increase of both DA and DOPAC levels after treatment with NPY. This effect was reproduced by NPY13-36 in cortical tissue, whereas, in the sub-cortical regions, NPY13-36 only reproduced the effects of NPY on the DOPAC levels. Less consistent effects were found on the NA systems, in which NA levels showed a tendency to increase following low, and decrease after high doses of NPY. These effects were largely reproduced by NPY13-36. In addition, NPY increased tissue levels of MHPG in frontal cortical tissue in a dose-related manner. The brain 5-HT systems were not affected.
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TL;DR: Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, and work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems.
Abstract: Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY) fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties.(ABSTRACT TRUNCATED AT 400 WORDS)
239 citations
TL;DR: I. Biosynthesis of TRH and Other pro-TRH-Derived Peptide Receptors, and the role of PCs and CPs and Neuropeptide and catecholamine regulation of Pro- TRH biosynthesis and processing.
Abstract: I. Introduction II. Biosynthesis of TRH and Other pro-TRH-Derived Peptides A. Biosynthesis and processing of pro-TRH B. Intracellular sites of pro-TRH processing C. Tissue-specific processing of pro-TRH D. The role of PCs and CPs E. Neuropeptide and catecholamine regulation of Pro-TRH biosynthesis and processing F. Glucocorticoids modulate the biosynthesis and processing of pro-TRH G. Leptin regulates pro-TRH biosynthesis III. Function of TRH A. The HPT axis B. Extrahypophysiotropic TRH IV. Function of non-TRH pro-TRH-Derived Peptides A. prepro-TRH160–169 (pST10) B. prepro-TRH178–199 (pFE22) C. prepro-TRH178–185 and prepro-TRH186–199 (pFQ7 and pSE14) D. prepro-TRH53–74 (pFT22) E. prepro-TRH83–106 (pEH24) and prepro-TRH208–255 F. TRH-Gly V. Non-TRH pro-TRH-Derived Peptides Outside of the CNS VI. TRH and Other pro-TRH-Derived Peptide Receptors A. The TRH receptor B. The prepro-TRH160–169 (pST10) receptor VII. TRH Degradation VIII. Concluding Remarks
185 citations
TL;DR: A comprehensive review of central distribution of NPY and its receptors, co‐localizations and interactions with other neuromessengers, genetic aspects, pharmacological and physiological actions, influence on neuroendocrine functions, and possible involvement in various neuropsychiatric illnesses are given.
Abstract: Neuropeptide Y (NPY) was first discovered and characterized as a 36-amino-acid peptide neurotransmitter in 1982. It is widely distributed in the central nervous system, with particularly high concentrations within several limbic and cortical regions. A number of co-localizations with other neuromessengers such as noradrenaline, somatostatin, and gamma-aminobutyric acid have been demonstrated. A large number of physiological and pharmacological actions of NPY have been suggested. Recent clinical data also suggest the involvement of NPY in several neuropsychiatric illnesses, particularly in depressive and anxiety states. This article gives a comprehensive review of central distribution of NPY and its receptors, co-localizations and interactions with other neuromessengers, genetic aspects, pharmacological and physiological actions, influence on neuroendocrine functions, and possible involvement in various neuropsychiatric illnesses.
175 citations
TL;DR: Results and the use of two selective radioligands demonstrate further the discrete, differential distribution of the Y1 and Y2 receptor subtypes in the rat brain.
Abstract: The peptide YY derivatives [Leu31,Pro34]PYY and PYY3-36 are highly selective Y1 and Y2 agonists, devoid of activity on the Y3 receptor subtype [Dumont et al. (1994) Molec. Brain Res., 26:3220-3324]. These selective ligands were iodinated and used to evaluate the respective quantitative autoradiographic distribution of the Y1 and Y2 receptor subtypes in the rat brain, excluding a potential contamination from Y3 receptor. Specific [125I][Leu31,Pro34]PYY (Y1), and [125I]PYY3-36 (Y2) binding sites are detected in various brain regions, but each showed a differential distribution profile. Y1/[125I][Leu31,Pro34]PYY sites are especially concentrated in superficial layers of the cortex, the olfactory tubercle, islands of Calleja, tenia tecta, molecular layer of the dentate gyrus, several thalamic nuclei, and the posterior part of the medial mammaliary nucleus. These areas generally contained only low densities of Y2/[125I]PYY3-36 binding sites. In contrast, [125I]PYY3-36 binding is most abundant in multiple other regions including the lateral septum, piriform cortex, triangular septal nucleus, bed nucleus of the stria terminalis, oriens layer and stratum radiatum of the dorsal hippocampus, ventral tegmental area, substantia nigra, dorsal raphe nucleus, and the granular cell layer of the cerebellum. Few areas of the rat brain contained significant amounts of both [125I][Leu31,Pro34]PYY and [125I]PYY3-36 binding sites such as the anterior olfactory nuclei, oriens layer and stratum radiatum of the ventral hippocampus, nucleus tractus solitarius, area postrema, and inferior olive. Taken together, these results and the use of two selective radioligands demonstrate further the discrete, differential distribution of the Y1 and Y2 receptor subtypes in the rat brain.
160 citations
TL;DR: Under conditions that result in low D2 receptor affinity, D3 specificity was examined in vitro at 15 days with (±) 7-OH-DPAT, which produced comparable effects to those observed in vivo.
Abstract: Dopamine synthesis modulation by the D2-family agonist (+/-)-7-OH-DPAT was explored in striatum, accumbens, and prefrontal cortex of 10-40 day old rats using the gamma-butyrolactone (GBL) autoreceptor model. GBL produced an age-dependent increase in dopamine synthesis that was inhibited by (+/-) 7-OH-DPAT (0.1-13.5 mg/kg) at all ages and antagonized by eticlopride in the nucleus accumbens and striatum. The ID50 of (+/-) 7-OH-DPAT increased with age, suggesting decreased autoreceptor sensitivity with maturation. In prefrontal cortex, (+/-) 7-OH-DPAT inhibited synthesis between 10-30 days, with no evidence of autoreceptor function at 40 days. Dopamine synthesis was also inhibited with the D3/D2 agonist quinpirole at 15 days of age in vivo and yielded similar results to those obtained with (+/-) 7-OH-DPAT. Finally, under conditions that result in low D2 receptor affinity, D3 specificity was examined in vitro at 15 days with (+/-) 7-OH-DPAT, which produced comparable (yet more potent) effects to those observed in vivo. These findings illustrate D3 autoreceptor-like activity in ascending dopamine regions and provide further support for transient prefrontal cortex autoreceptor-like function that recedes by puberty.
148 citations
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TL;DR: It is found that the peptide isolated from brain extracts of a peptide amide that was thought to be PYY is a previously uncharacterized peptide, which is designated neuropeptide Y (NPY), which is structurally and biologically similar to vasoactive intestinal peptide (VIP) while PYY shows similarities to pancreatic polypeptides (PP).
Abstract: The C-terminal α-amide structure is a characteristic feature of many biologically active peptides1,2 Using a novel chemical method for the detection of peptide amides3, we have isolated two naturally occurring peptides, peptide HI (PHI) and peptide YY (PYY), from extracts of porcine intestine and have shown that these peptide amides represent previously unknown biologically active peptides4 PHI is structurally and biologically similar to vasoactive intestinal peptide (VIP)5 while PYY shows similarities to pancreatic polypeptide (PP)6 Preliminary studies indicated that PHI and PYY may both be present in brain as well as in intestine4 We report here the isolation from brain extracts of a peptide amide that was thought to be PYY However, we found that the peptide, while having distinct structural and biological similarities to both PYY and PP, is a previously uncharacterized peptide, which we designate neuropeptide Y (NPY)
2,264 citations
"Effects of centrally administered n..." refers background in this paper
...Introduction Neuropeptide Y (NPY) is a 36 amino acid peptide neuromessenger originally isolated from the porcine brain (Tatemoto et al., 1982)....
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...Neuropeptide Y (NPY) is a 36 amino acid peptide neuromessenger originally isolated from the porcine brain (Tatemoto et al., 1982)....
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1,188 citations
"Effects of centrally administered n..." refers background in this paper
...In the PNS, NPY is mainly co-localized with noradrenaline (NA) in postganglionic sympathetic neurons, and seems to potentiate postsynaptic responses to the amine transmitter while presynaptically inhibiting its release (Lundberg et al., 1982)....
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...NPY is present in high amounts in both the peripheral (PNS) (Lundberg et al., 1982) and the central nervous system (CNS) (Chronwall et al....
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...NPY is present in high amounts in both the peripheral (PNS) (Lundberg et al., 1982) and the central nervous system (CNS) (Chronwall et al., 1985) of mammals....
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TL;DR: The extremely high concentrations and widespread distribution of neuropeptide Y in the central nervous system suggests a number of important physiological roles for this neurotransmitter candidate.
1,097 citations
"Effects of centrally administered n..." refers background in this paper
...In the brain, NPY is unevenly distributed, with highest concentrations in the hypothalamus, limbic areas, brain stem nuclei, and the cortex (Chronwall et al., 1985)....
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...Numerous CNSeffects of NPY have been suggested (for a review, see Wahlestedt et al., 1989)....
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...NPY is present in high amounts in both the peripheral (PNS) (Lundberg et al., 1982) and the central nervous system (CNS) (Chronwall et al., 1985) of mammals....
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TL;DR: The findings indicate that central catecholamine neurons can be subdivided into distinct sub-groups based upon the coexistence of a specific peptide.
856 citations
TL;DR: A C-terminal portion appears to be sufficient for exerting the prejunctional effect of NPY and PYY, while the whole sequence seems to be required for post- junctional effects.
657 citations