Pharmacological studies of voltage-sensitive Ca2+-channels involved in the release of vasoactive intestinal peptide evoked by K+ in mouse cerebral cortical slices.
Three types of voltage-sensitive Ca2+-channels, denominated T, N and L, have recently been identified in the nervous system. This classification is based on both the electrophysiological and pharmacological properties of each type of channel. The increase in free intracellular Ca2+ concentration that results from the opening of voltage-sensitive Ca2+-channels triggers various cellular processes. One such process is the depolarization-induced release of neurotransmitters. Owing to the rather selective sensitivity of each type of voltage-sensitive Ca2+-channel to certain antagonists, attempts have recently been carried out to determine which of the T, N or L channels mediates neurotransmitter release. In the present study we have applied such a strategy to the study of the release of vasoactive intestinal peptide from mouse cerebral cortical slices. The release of vasoactive intestinal peptide evoked by K+ 20 mM is inhibited in a concentration-dependent manner by Co2+, Ni2+ and Mn2+ while it remains unaffected by diltiazem 20 microM, nifedipine 10 microM, omega-conotoxin 1 microM and Cd2+ up to 100 microM. Such a pharmacological profile indicates that voltage-sensitive Ca2+-channels of the N and L types are not involved in the release of vasoactive intestinal peptide. These observations are in contrast to what has been described for amine release in the central nervous system, which appears to be mediated by voltage-sensitive Ca2+-channels of the N type.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
J L
JL
Département de Pharmacologie, Centre Médical Universitaire, Geneva, Switzerland.
Magistretti
P J
PJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002413:Cations, Divalent / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011188:Potassium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D011188:Potassium