Differential sensitivity to blockade by 4-aminopyridine of presynaptic receptors regulating [3H]acetylcholine release from rat hippocampus.
The inhibitory effect of an adenosine analogue, R-N6-phenylisopropyl adenosine (R-PIA), of the cholinergic agonist carbachol, and of morphine on 3H efflux from [3H]choline-labeled field-stimulated rat hippocampal slices was compared with that produced by two inhibitors of N- and L-type Ca2+ channels, omega-conotoxin (CgTx; conotoxin GVIA) and cadmium chloride. 4-Aminopyridine (4-AP) caused a dose-dependent increase in evoked transmitter release, with a maximal effect (an almost threefold increase) at 100 microM. 4-AP (100 microM) did not affect the actions of CgTx, cadmium chloride, and R-PIA but almost abolished the effect of carbachol and morphine. The present results indicate that presynaptic muscarinic and opiate receptors reduce acetylcholine release by a mechanism that is somewhat different from that used by adenosine A1 receptors. Furthermore, the results indicate that presynaptic A1 receptors on hippocampal cholinergic neurons do not primarily regulate 4-AP-dependent potassium channels, but that they might act directly on a Ca2+ conductance.
Fredholm
B B
BB
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
D015761:4-Aminopyridine / Q000494:pharmacology*; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009994:Osmolar Concentration; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D014316:Tritium; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; D002104:Cadmium; D014316:Tritium; D010660:Phenylisopropyladenosine; D009020:Morphine; D002217:Carbachol; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D019256:Cadmium Chloride; D000109:Acetylcholine