title: Cyclic AMP enhances acetylcholine (ACh)-induced ion fluxes and catecholamine release by inhibiting Na+, K(+)-ATPase and participates in the responses to ACh in cultured bovine adrenal medullary chromaffin cells.
abstract: The effects of cyclic AMP (cAMP) on intracellular Na+ concentration ([Na+]i), membrane depolarization and intracellular Ca2+ concentration ([Ca2+]i) and the involvement of cAMP in acetylcholine (ACh)-induced such cellular events and catecholamine (CA) release were studied in cultured bovine adrenal medullary chromaffin cells. 8-Bromo-cyclic AMP (8Br-cAMP) and forskolin caused a rise in [Na+]i, membrane depolarization and a rise in [Ca2+]i and potentiated these responses and CA release to ACh. The effects of 8Br-cAMP or forskolin on ACh-induced changes of but not on basal level of [Na+]i, membrane potential and [Ca2+]i were blocked by tetrodotoxin (TTX, 1 microM). In Na+ deprivated medium, forskolin failed to produce an increase in basal [Ca2+]i level and to potentiate ACh-induced rise. The similar results as in 8Br-cAMP and forskolin were obtained using ouabain, and 8Br-cAMP or foskolin produced no further effects in the presence of ouabain. Inhibitors of cAMP-dependent protein kinase not only blocked the effects of 8Br-cAMP and forskolin on membrane depolarization, [Ca2+]i rise and CA release, but also reduced these responses to ACh. From the similarity between the effects of cAMP and those of ouabain on the cellular events and the counteraction of the effects of cAMP by ouabain, it may be suggested that cAMP produces its effects on ion fluxes and CA release probably via an inhibition of Na+, K(+)-ATPase in intact chromaffin and cAMP may participate in the responses to ACh.
authors: Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
authors: K
authors: K
authors: Morita
authors: N
authors: N
authors: Minami
authors: T
authors: T
authors: Suemitsu
authors: T
authors: T
authors: Miyasako
authors: T
authors: T
authors: Dohi
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013449:Sulfonamides; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011950:Receptors, Cholinergic; D013449:Sulfonamides; D013873:Thionucleotides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D013779:Tetrodotoxin; D010042:Ouabain; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D000109:Acetylcholine; D002118:Calcium