Possible neuronal origin of ATP release evoked by forskolin and ouabain from guinea-pig atrial segments.
The characteristics of ATP release evoked by forskolin and ouabain from atrial segments of guinea-pig were evaluated under electrical stimulation. Forskolin (1 microM) produced a massive release of ATP together with a positive inotropic response. Both 30 microM W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide.HCI), a calmodulin antagonist, and 30 microM vinblastine, a mitotic inhibitor, markedly inhibited the evoked release of ATP without affecting the evoked contraction. However, 100 microM N-ethylmaleimide abolished completely the basal and drug-evoked ATP release and further the evoked contraction. Both the ATP release and contraction evoked by ouabain (3 microM) were similarly affected by W-7, vinblastine and n-ethylmaleimide. The release of ATP, but not the contraction, evoked by forskolin was strongly suppressed by 10 microM okadaic acid, a protein phosphatase inhibitor. The suppression by okadaic acid of the evoked release was thoroughly antagonized in the presence of 0.01 microM PMA (phorbol 12-myristate 13-acetate), but not 10 microM H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine). These results suggest that forskolin, like ouabain, may dominantly cause the neuronal release of ATP from cardiac adrenergic nerves, although the possible participation of release from muscular sources cannot be ignored.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid; D010042:Ouabain / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D002147:Calmodulin; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D013449:Sulfonamides; D005576:Colforsin; D019319:Okadaic Acid; D010042:Ouabain; D014747:Vinblastine; C017967:W 7; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases