Role of omega-conotoxin-sensitive calcium channels in inositolphosphate production and noradrenaline release due to potassium depolarization or stimulation with carbachol.
omega-Conotoxin GVIA (CTX) has been used to assess the role of voltage-sensitive Ca2+ channels involved in inositolphosphate (InsP) production and in noradrenaline (NA) release from washed brain homogenates. Stimulation was performed by depolarization with high [K+] and by the M-cholinergic agonist carbachol. In chicken brain CTX (1 mumol/l and less) nearly completely inhibited both InsP production and NA release due to high [K+]. The peptide depressed InsP production moderately but NA release largely when evoked with carbachol. In rat brain inhibition by CTX of InsP production or NA release was weak or even absent independent of the mode of stimulation. Independent of species or test system, the dihydropyridine derivative nitrendipine (1 mumol/l and above) was inactive. Because of its preferential CTX sensitivity chicken brain is particularly suitable to study the role of voltage-sensitive Ca2+ channels in presynaptic events. Here InsP production, like NA release, depends on entry of extracellular Ca2+ nearly completely when evoked by depolarization. When evoked by way of cholinergic M-receptor stimulation, InsP production is triggered by a second pathway in addition to the CTX-sensitive Ca2+ entry.
Hofmann
F
F
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
Habermann
E
E
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002645:Chickens; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D007295:Inositol Phosphates; D009467:Neuromuscular Depolarizing Agents; D010456:Peptides, Cyclic; D013779:Tetrodotoxin; D002217:Carbachol; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D011188:Potassium; D009638:Norepinephrine