Relationship of calcium and adenylate cyclase messenger systems in rat brain synaptosomes.
The effects of cyclic AMP on the rise in cytosolic free calcium concentration, [Ca2+]i, after stimulation with 15 mM K+ in rat brain synaptosomes were investigated. The fluorescent chelating agent Quin-2 was employed to monitor alterations of K+-evoked [Ca2+]i. Under normoxic conditions, clonidine (1, 10 microM), an alpha 2-adrenoceptor agonist, decreased the 15 mM K+-evoked [Ca2+]i. Although yohimbine (1, 10 microM), an alpha 2-adrenoceptor antagonist, had little or no effect on K+-evoked [Ca2+]i, the inhibitory effects of clonidine were blocked by yohimbine. 8-Bromo cyclic AMP, a cyclic AMP analogue, (50-500 microM), increased K+-evoked [Ca2+]i in a dose-dependent manner. The addition of cyclic AMP analogues subsequent to clonidine treatment reversed the clonidine-induced suppression of K+-evoked [Ca2+]i. On the other hand, under hypoxic conditions, K+-evoked [Ca2+]i was reduced by about 50-60%. 8-Bromo cyclic AMP and the adenylate cyclase activators, yohimbine (1-10 microM) and isoproterenol, a beta-adrenoceptor agonist, (0.1-10 microM), transiently reversed the reduction of the K+-evoked [Ca2+]i caused by hypoxia. These results indicate that the activation of alpha 2-adrenoceptor produces a rapid, sustained decrease in [Ca2+]i which may be due to a decrease in the levels of intracellular cyclic AMP. In addition, the increase in cellular levels of cyclic AMP reversed the reduction of the Ca2+ response to high K+ stimulation caused by hypoxia. If this is so, there is the possibility that increased cyclic AMP might improve the hypoxic damage.
Okada
M
M
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Mine
K
K
Fujiwara
M
M
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D013574:Synaptosomes / Q000378:metabolism / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003000:Clonidine; D011188:Potassium; D002118:Calcium