Showing papers on "Kainate receptor published in 1984"
TL;DR: The results demonstrate that NMDA receptors present in hippocampal region CA1 are not necessary for normal synaptic transmission, but are involved in the initiation of long-term synaptic plasticity.
892 citations
TL;DR: An evaluation of investigations designed to elucidate regulatory mechanisms at acidic amino acid binding sites is made; hypotheses such as the Ca2+-activated protease hypothesis of long-term potentiation are assessed in terms of the new binding site/receptor classification scheme.
815 citations
TL;DR: It is reported that [3H]-D-AP5 binds specifically to rat brain membranes, that the hippocampus and cerebral cortex are enriched in these sites relative to other brain areas and that L-glutamate has higher affinity for these receptors than have all other transmitter candidates tested.
Abstract: Electrophysiological studies indicate the existence of several types of receptors for excitatory amino acids. Thus, responses induced by N-methyl-D-aspartate (NMDA) are potently and selectively blocked by D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), while responses induced by such agonists as kainate and quisqualate are relatively resistant to this antagonist. Evidence is mounting that excitatory amino acid receptors are involved in synaptic excitation in many regions of the central nervous system (see refs 1 and 4 for reviews). Although the identity of the transmitter(s) acting at these receptors remains uncertain, L-aspartate has been considered the most likely transmitter at NMDA receptors and L-glutamate at kainate/quisqualate receptors. Other endogenous acidic amino acids proposed as possible transmitters include a range of sulphur-containing amino acids and the tryptophan metabolite, quinolinic acid. Ligand-binding studies offer a means not only of assessing receptor densities in different brain regions but also of comparing affinities of transmitter candidates for these receptors. However, to avoid difficulties of interpretation arising from the use of ligands which bind to more than one type of receptor, such as [3H]-L-glutamate and [3H]-L-aspartate (for example, refs 8-12), ligands with high receptor selectivity are required. Here, we report that [3H]-D-AP5 binds specifically to rat brain membranes, that the hippocampus and cerebral cortex are enriched in these sites relative to other brain areas and that L-glutamate has higher affinity for these receptors than have all other transmitter candidates tested.
295 citations
TL;DR: It is suggested that L‐glutamate acts as a mixed agonist at both NMDA and non‐NMDA receptors and can explain the results of previous experiments that failed to demonstrate a membrane resistance change during L‐ glutamate‐induced depolarizations.
Abstract: Neurones from the ventral half of mouse embryo spinal cord were grown in tissue culture and voltage clamped with two micro-electrodes. The current-voltage relation of responses evoked by brief pressure applications of excitatory amino acids was examined over a membrane potential range of -100 to +70 mV. Three types of current-voltage relation were observed. Responses to kainic and quisqualic acids were relatively linear within +/- 20 mV of the resting potential. N-methyl-D-aspartate (NMDA) and L-aspartic acid responses had a negative slope conductance at membrane potentials more negative than -30 mV. In contrast, over the same potential range the slope conductance of responses evoked by L-glutamic and L-homocysteic acids was close to zero. The membrane potential-chord conductance relation of the ionic mechanism activated by excitatory amino acids, derived using the driving force for ionic current, showed two types of behaviour. The conductance linked to NMDA receptors was highly voltage sensitive and increased on depolarization; a much weaker voltage sensitivity was observed for responses evoked by kainic and quisqualic acids. L-glutamic and L-homocysteic acid responses behaved as though due to simultaneous activation of both NMDA and either kainate or quisqualate receptors. In the presence of the NMDA receptor antagonist (+/-)-2-aminophosphonovaleric acid (2-APV) the response to L-glutamate became less voltage sensitive and resembled responses evoked by kainate or quisqualate. Simultaneous activation of both conductance mechanisms by mixtures of kainate and NMDA produced current-voltage and membrane potential-chord conductance relations similar to those of L-glutamate. The voltage sensitivity of the L-glutamate response was inversely related to the dose; for low doses of L-glutamate the slope conductance of responses recorded near the resting potential was close to zero. However, larger doses of L-glutamate evoked responses with a voltage sensitivity similar to that of kainate. We suggest that L-glutamate acts as a mixed agonist at both NMDA and non-NMDA receptors. This can explain the results of previous experiments that failed to demonstrate a membrane resistance change during L-glutamate-induced depolarizations.
276 citations
TL;DR: Two main conclusions can be drawn from these experiments: kainate activates the hippocampus from a very early age probably by means of specific receptors present in this structure and the limbic syndrome will only be produced by the toxin once the limbsic circuitry--including in particular the amygdaloid complex--is activated by the procedure i.e. after the third week of age.
202 citations
TL;DR: Sodium channels and receptors to serotonin and kainate were ‘transplanted’ from human brain into frog oocytes, by isolating messenger RNA from a fetal brain and injecting it into Xenopus laevis oocytes.
Abstract: Sodium channels and receptors to serotonin and kainate were ‘transplanted’ from human brain into frog oocytes, by isolating messenger RNA from a fetal brain, and injecting it into Xenopus laevis oocytes. The mRNA was translated by the oocyte and induced the appearance of functional receptors and channels in its membrane. This approach renders drug- and voltage-operated channels of the human brain more amenable to detailed study.
182 citations
TL;DR: The tonic excitation of motoneurones which occurs during swimming appears to be mediated via an endogenous excitatory amino acid transmitter which acts on NMDA and kainate receptors, and when applied to intact animals during swimming both 2‐3 mM‐cis‐2,3‐piperidine dicarboxylic acid (PDA) and 0.5 mM‐gamma‐D‐glutamylglycine (DGG) selectively blocked the ton
Abstract: Bath application of N-methyl-D-aspartate (NMDA), kainate or quisqualate to Xenopus embryos depolarized spinal cord motoneurones and reduced their input resistance in both normal salines and salines containing 20 mM-Mn2+ and 0.5 mM-Ca2+, or 2 X 10(-6) M-tetrodotoxin. This suggests that motoneurones possess all three types of excitatory amino acid receptor. These receptors have similar specificities to excitatory amino acid antagonists as those occurring in adult frog and cat spinal cords. Application of 30-40 microM-NMDA or 5-6.5 microM-kainate to the medium bathing spinalized embryos can cause a sustained patterned motor output similar to that of swimming evoked by natural stimulation of intact animals. At these concentrations NMDA and kainate depolarized motoneurones by 19.0 +/- 1.80 (mean +/- S.E. of mean) and 18.0 +/- 2.00 mV respectively and decreased their input resistance by 23.0 +/- 2.82% and 24.0 +/- 3.46%. These changes are similar to those associated with the tonic excitation which motoneurones receive during naturally evoked swimming. Bath application of 5-8 microM-quisqualate to spinal embryos can also cause a sustained motor output. However, this was different to that evoked by NMDA and kainate and was inappropriate for swimming. When applied to intact animals during swimming both 2-3 mM-cis-2,3-piperidine dicarboxylic acid (PDA) and 0.5 mM-gamma-D-glutamylglycine (DGG) selectively blocked the tonic excitation of motoneurones and in doing so abolished the motor output of the spinal cord. 50-200 microM-2-amino-5-phosphonovaleric acid reduced the tonic excitation but to a lesser extent than either PDA or DGG. The tonic excitation of motoneurones which occurs during swimming therefore appears to be mediated via an endogenous excitatory amino acid transmitter which acts on NMDA and kainate receptors.
143 citations
TL;DR: Xenopus laevis oocytes injected with poly(A)+ mRNA extracted from rat brain became sensitive to serotonin, glutamate, kainate, acetylcholine and γ-aminobutyrate, and it appears that mRNA from rat head contains translationally active messengers which code for various neurotransmitter receptors.
Abstract: Xenopus laevis oocytes injected with poly (A)$^{+}$ mRNA extracted from rat brain became sensitive to serotonin, glutamate, kainate, acetylcholine and $\gamma $-aminobutyrate. Application of these substances to mRNA-injected oocytes elicited membrane currents. The glutamate- and acetylcholine-induced currents usually showed oscillations, while the kainate current was smooth. The current oscillations during glutamate application reversed direction at about the chloride equilibrium potential (--24 mV), but the reversal potential for the kainate current was close to 0 mV. The current-voltage relation for the glutamate-induced current oscillations showed strong rectification at hyperpolarized potentials, while that for the kainate current was nearly linear. In some oocytes, glutamate elicited smooth membrane currents, with oscillations either absent, or appearing after a delay. The reversal potential of this component was close to 0 mV, and was clearly different from that of the oscillatory component. The appearance of glutamate and kainate sensitivity in the oocyte membrane is due to the translation of the foreign messenger RNA, and not to activation of the oocytes9 own genome, because oocytes still become sensitive when transcription is prevented by enucleation or by treatment with actinomycin D. It appears that mRNA from rat brain contains translationally active messengers which code for various neurotransmitter receptors. When this mRNA is injected into Xenopus oocytes, the messengers are translated and receptors are inserted into the oocyte membrane, where they form functionally active receptor-channel complexes.
117 citations
TL;DR: Retinal neurons were enzymatically and mechanically dissociated from adult skate retinas and maintained in cell culture for up to 14 days, and the glutamate analogues, kainate and quisqualate, induced certain morphological changes, most notably a retraction of cell processes and the appearance of blebs on the cell surface.
Abstract: Retinal neurons were enzymatically and mechanically dissociated from adult skate retinas and maintained in cell culture for up to 14 days. Intracellular recordings were made from isolated horizontal and bipolar cells while neurotransmitters were applied via pressure ejection. L- Glutamate, quisqualate, kainate, and gamma-amino-butyric acid (GABA), when applied to horizontal cells, produced large (60 to 70 mV), long- lasting depolarizations. These responses appear to consist of at least two components: a graded depolarization and a Ca++-dependent regenerative component. As regards bipolar cells, L-glutamate and its analogues depolarized about 30% of the cells tested, while GABA hyperpolarized most of these neurons. Both agents acted on bipolar cells by increasing conductance. Repeated applications of L-glutamate, quisqualate, kainate, and GABA to horizontal cells produced no desensitization, but in these circumstances the glutamate analogues, kainate and quisqualate, induced certain morphological changes, most notably a retraction of cell processes and the appearance of blebs on the cell surface.
98 citations
TL;DR: The results suggest that receptors for excitatory amino acids can be targets for the actions of barbiturates and alcohols on the central nervous system, and may mediate some of the anesthetic and hypnotic effects of these drugs.
92 citations
TL;DR: In this article, the structure-activity relations of dipeptides related to gamma-D-glutamylglycine have been investigated with respect to the ability of these substances to antagonize depolarizing responses of frog motoneurones in vitro to N-methyl-d-aspartate, kainate and quisqualate.
TL;DR: It is concluded that actions at s‐ but not κ‐, opiate receptors are responsible for the NMA antagonism observed with benzomorphans.
Abstract: Using the technique of microelectrophoresis in pentobarbitone-anaesthetized cats and rats, the effects of benzomorphans, with known actions at sigma- and kappa- opioid receptors, were tested on responses of spinal neurones to amino acids and acetylcholine. The racemic mixture and both enantiomers of the sigma opiate receptor agonist, N-allylnormetazocine (SKF 10, 047), and the dissociative anaesthetic, ketamine, reduced or abolished excitation evoked by N-methyl-aspartate (NMA) with only small and variable effects on responses to quisqualate or kainate. (+)-SKF 10, 047 was 1.2 +/- 0.7 times more potent than the (-)-enantiomer in antagonizing NMA. On Renshaw cells, (+)-SKF 10, 047 enhanced responses to acetylcholine whereas the (-) enantiomer produced only a small reduction. The kappa- opiate receptor agonist, ethylketocyclazocine, had no selective effects on responses to amino acids or to acetylcholine. We conclude that actions at sigma- but not kappa-, opiate receptors are responsible for the NMA antagonism observed with benzomorphans.
TL;DR: The responses of granule cells to glutamate, aspartate, N‐methyl‐D‐aspartate (NMDA), quisqualate and kainate applied by ionophoresis were studied with intracellular electrodes using an in vitro hippocampal slice preparation to support the hypothesis that both the transmitter released by the medial perforant path and exogenously applied glutamate are unlikely to interact with NMDA receptors.
Abstract: The responses of granule cells to glutamate, aspartate, N-methyl-D-aspartate (NMDA), quisqualate and kainate applied by ionophoresis on to their dendrites in the middle molecular layer of the dentate gyrus were studied with intracellular electrodes using an in vitro hippocampal slice preparation. On passive depolarization 75% of the granule cells displayed anomalous rectification, which persisted in the presence of TTX and TEA but was eliminated by Co2+ or the intracellular injection of Cs+. Short ionophoretic applications of all the excitatory amino acids evoked dose-dependent depolarizations that were highly localized: movement of the ionophoretic electrode by as little as 10 microns could substantially change the size of the response. The depolarizations evoked by glutamate, asparatate, quisqualate and kainate were unaffected by TTX and Co2+. The depolarization evoked by NMDA was unaffected by TTX but markedly reduced by Co2+. Following intracellular injection of Cs+, neurones could be depolarized to +30 mV and the depolarizations produced by glutamate, quisqualate, NMDA and kainate reversed. The reversal potentials (E) were Eglutamate: -5.6 +/- 0.4 mV; ENMDA: 1.8 +/- 1.9 mV; Equisqualate: -3.9 +/- 1.9 mV; Ekainate: -4.6 +/- 2.0 mV. The excitatory post-synaptic potential (e.p.s.p.) evoked by stimulation of the medial perforant path could also be reversed and Ee.p.s.p. was -5.5 +/- 1.1 mV. The 6 mV difference between ENMDA and the equilibrium potential for the other exogenously applied excitatory amino acids and the statistically significant difference between ENMDA and Ee.p.s.p. (P less than 0.005; d.f.: 7) is consistent with our earlier hypothesis that both the transmitter released by the medial perforant path and exogenously applied glutamate are unlikely to interact with NMDA receptors.
TL;DR: The observed changes in neurotransmitter receptors in HE afford a feasible pathophysiological basis for the mediation of the neural inhibition of HE.
TL;DR: The particular vulnerability of hippocampal CA3/CA4 neurons to intracerebroventricularly administered kainate did not occur in rats until postnatal day 16, and no correlation appears between kainates/glutamate-induced behavioral changes and their neurodegenerative potency.
TL;DR: The results indicate that uptake or other mechanisms decrease the apparent sensitivity of these cells in the intact retina to L-glutamate by 25-200 times, and suggest that L- glutamate is more likely a photoreceptor transmitter than L-aspartate.
TL;DR: The dissimilar patterns of extra-hippocampal damage in immature and adult rabbits suggest that mature and immature animals have differential sensitivity to kainates, different types of kainate binding sites, and/or different distributions ofKainate receptors.
TL;DR: The effect of γ-d-glutamylaminomethylsulphonic a cid (GAMS) on sound-induced seizures has been assessed in DBA/2 mice and the involvement of ‘kainate” and ‘quisqualate’ receptors in the generation and propagation of seizures is discussed.
TL;DR: Two novel dipeptides are potent and selective N-methyl-D-aspartate receptor antagonists and specifically depress polysynaptic excitation in the cat, rat and frog spinal cords, and are more effective as depressants of monosynaptic than of polysyn synaptic excitation.
TL;DR: The relative potencies of these compounds and the vulnerability of the different cell types to their neurotoxic effects are in accordance with the predictions of the excitotoxic hypothesis and therefore do not support a special mechanism for kainate neurotoxicity in the cerebellum.
TL;DR: Evidence that calcification of cerebral tissue is closely associated with neurodegenerative processes is provided and kainate may serve as a tool to elucidate the mechanism of brain calcification is shown.
Abstract: Following local application of kainic acid, changes in the contents of Na+, K+, Ca2+, and Mg2+ of the striatum, cerebellum, and hippocampus of the rat were observed at various times after surgery. Within 1 h the levels of K+ decreased 20% whereas the levels of Na+ and Ca2+ increased at least 50% and 20%, respectively. These changes persisted for more than 8 weeks. Ca2+ levels rose further, to more than 10-fold during 8 weeks. The Mg2+ levels were slightly and only transiently decreased. Unilateral injections of kainate into the striatum affected the contents of these cations not only in this area, but also in the overlying cerebral cortex, the olfactory tubercle, and the ipsilateral substantia nigra. The Ca2+ increases were less when rats were kept on a diet deficient in Ca2+ and vitamin D. 45Ca2+, intravenously administered, accumulated significantly more in the kainate-lesioned striatum and substantia nigra than in the homotopic contralateral areas. Electron microscopic examination of the localization of Ca2+ with the oxalate-pyroantimonate technique showed the appearance of extracellularly located deposits and the accumulation of Ca2+ in (possibly degenerating) myelinated axons in kainate-lesioned striata. This study provides evidence that calcification of cerebral tissue is closely associated with neurodegenerative processes and shows that kainate may serve as a tool to elucidate the mechanism of brain calcification. The results are discussed in relation to idiopathic calcinosis (striopallidodentate calcinosis, Fahr's disease).
TL;DR: The finding that folate and kainate produced their effects in the absence of a detectable effect on the antidromic population spike suggests a mechanism of action other than neuronal depolarization.
TL;DR: The 8 brain constituents possessing excitatory properties displayed a receptor specificity similar to either that of N-methyl-D-aspartate or glutamate but not of kainate or quisqualate, which is discussed in relation with the problem of the identification of brain exciteatory neurotransmitters.
TL;DR: The results suggest that glutamate may activate a receptor directly linked to Ca2+ channels, whereas kainate may indirectly modulate the intracellular disposition of Ca2+.
TL;DR: It is concluded that L-aspartate (and/or glutamate) might interact with postsynaptic receptors in the ganglion cell membrane and mimics the action of the natural photoreceptor transmitter.
TL;DR: It is suggested that a reduced efficiency at excitatory synapses utilising N-methyl-D,L-aspartate receptors contributes to that part of the pharmacological spectrum common to both arylcyclohexylamines and dioxolanes.
TL;DR: The response to L-glutamate, ibotenate and carbachol are dependent on sodium, the responses to quisqualate and AMPA are mainly sodium dependent, possibly with a small calcium component, and the kainate response in normal Ringer is largely sodium dependent but in sodium-free Ringer calcium can completely substitute for sodium.
TL;DR: It is concluded that GABAB sites in the IPN are primarily located on presynaptic terminals of the habenula input.
TL;DR: The onset and developmental pattern of kainate effects were determined in isolated embryonic and posthatching chick neural retinas exposed to KA in vitro, and results are consistent with those reported for a variety of neonatal and adult retinas treated with kainates in vivo.
TL;DR: Kainic acid produces lesions in the chick retina when injected intravitreally to ascribe L-glutamate and L-aspartate receptors to specific neuronal populations, and specific binding to membranes from retinas treated with different doses of KA was measured.