Caffeine-induced transmitter release is mediated via ryanodine-sensitive channel.
An isolated clone PC12-37 of rat pheochromocytoma PC12 cells, which lacks ryanodine-sensitive Ca2+ channel, responds to depolarization and to agonist activation and triggers [3H]dopamine ([3H]DA) release. A caffeine-stimulated transmitter release, while present in the parental PC12 cell line, is completely abolished in PC12-37 cells. In contrast, caffeine-induced Ca2+ influx in PC12-37 cells is similar to that observed in PC12 cells, indicating that caffeine-induced CA2+ influx is neither mediated by caffeine-induced Ca2+ release nor contributes to the caffeine-induced secretion. These results show (a) a tight coupling between caffeine activation of a ryanodine-sensitive Ca2+ store and transmitter release, (b) no significant involvement of the ryanodine-sensitive Ca2+ channel in depolarization- and agonist-mediated transmitter release, and (c) exclude a major role for caffeine-mediated Ca2+ entry in the caffeine-activated secretion.
Avidor
T
T
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Clementi
E
E
Schwartz
L
L
Atlas
D
D
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology*
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002395:Catecholamines; D018377:Neurotransmitter Agents; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium; D004298:Dopamine