Stimulation-evoked Ca2+ fluxes in cultured bovine adrenal chromaffin cells are enhanced by forskolin.
Forskolin, 1 microM, increased acetylcholine (ACh)-stimulated 45Ca uptake by chromaffin cells. The stimulatory effects of forskolin decreased with increasing concentration of ACh. The attenuation of the effect of forskolin on 45Ca uptake as a function of ACh concentration correlated well with changes in the forskolin effect on ACh-evoked catecholamine (CA) release. Forskolin increased excess KCl- and veratrine-evoked CA release and 45Ca uptake. Forskolin by itself stimulated 45Ca efflux and enhanced ACh-, excess KCl-, and veratrine-stimulated 45Ca efflux. High doses of forskolin inhibited both ACh-evoked 45Ca uptake and CA release. The inhibitory action of forskolin was specific to receptor-mediated response because excess KCl- and veratrine-stimulated 45Ca uptake and CA release were not inhibited. Forskolin, 0.3-30 microM, dose-dependently increased caffeine-stimulated CA release and 45Ca efflux in the absence of Ca2+ in the medium, and the effects were mimicked by dibutyryl cyclic AMP. These results suggest that cyclic AMP increases stimulation-induced CA release by enhancing calcium uptake across the plasma membrane and/or altering calcium flux in an intracellular calcium store.
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology
D005576:Colforsin; D002110:Caffeine; D003994:Bucladesine; D011189:Potassium Chloride; D000242:Cyclic AMP; D014702:Veratrine; D000109:Acetylcholine; D002118:Calcium