Calcium channel antagonist peptides define several components of transmitter release in the hippocampus
| Autor: | B. Rivnay, G.P. Miljanich, D. Yamashiro, J. Ramachandran, J.R. Bell, R. Newcomb, S. Gaur |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Molecular Sequence Data Glutamic Acid Biology Hippocampal formation Pharmacology In Vitro Techniques Hippocampus omega-Conotoxins Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Norepinephrine Animals Conotoxin Amino Acid Sequence Neurotransmitter gamma-Aminobutyric Acid Aspartic Acid Neurotransmitter Agents Voltage-dependent calcium channel Calcium channel Glutamate receptor Antagonist Calcium Channel Blockers Agatoxin Rats chemistry Calcium Channels Peptides Neuroscience |
| Zdroj: | Neuropharmacology. 33(10) |
| ISSN: | 0028-3908 |
| Popis: | Summary The use of subtype-selective voltage-sensitive calcium channel (VSCC) antagonists has established that neurotransmitter release in mammalian brain is mediated by N-like and P-like VSCCs, and that other subtypes also contribute significantly. To determine the roles presynaptic VSCCs play in nervous system function and to evaluate the therapeutic potential of their selective inhibition, it is necessary to define further the contributions of VSCC subtypes to neurotransmitter release. The novel conopeptide, SNX-230 (ω-conopeptide MVIIC), has revealed a new VSCC subtype, the Q-type, in cerebellar granule cells. We have compared the effects of SNX-230 on release of tritiated d -aspartate ([3H] d -Asp; a non-metabolizable analog of glutamate), γ-aminobutyric acid ([3H]GABA), and norepinephrine ([3H]NE) from rat hippocampal slices to those of the N-type VSCC blocker, SNX-111 (ω-conopeptide MVIIA), and the P-type blocker, ω-agatoxin-IVA (AgalVA). SNX-230 blocks both [3H] d -Asp and [3H]GABA release completely, whereas AgaIVA blocks them potently but partially and SNX-111 has no effect. These results suggest that glutamate and GABA release are mediated by two VSCC subtypes, a P-type and another, perhaps Q-like. SNX-111 blocks [3H]NE release potently but partially, while SNX-230 blockade is complete, consisting of one very potent phase and one less potent phase. AgalVA also blocks [3H]NE release potently but partially. These results suggest that at least two VSCC subtypes, an N-type and a novel non-N-type, mediate NE release. Pair-wise combinations of the three ligands indicate that at least three pharmacologically distinct components comprise [3H]NE release in the hippocampus. |
| Databáze: | OpenAIRE |
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