Regulation of cyclic AMP levels by calcium in bovine adrenal medullary cells.
Both nicotine and histamine have been reported to increase cyclic AMP levels in chromaffin cells by Ca(2+)-dependent mechanisms. The present study investigated whether Ca2+ was an adequate and sufficient signal for increasing cyclic AMP in cultured bovine adrenal medullary cells. Depolarization with 50 mM K+ caused a two- to three-fold increase in cellular cyclic AMP levels over 5 min, with no change in extracellular cyclic AMP. This response was abolished by omission of extracellular Ca2+ and by 100 microM methoxyverapamil, and was unaffected by 1 microM tetrodotoxin and by 1 mM isobutylmethylxanthine. Veratridine (40 microM) also increased cellular cyclic AMP levels by two- to fourfold. This response was abolished by either methoxyverapamil or tetrodotoxin. The Ca2+ ionophore A23187 (10-50 microM) had little or no effect on cellular cyclic AMP levels. When the concentration of K+ used to depolarize the cells was reduced to 12-15 mM, the catecholamine release was similar to that induced by 50 microM A23187, and the cyclic AMP response was almost abolished. The results suggest that Ca2+ entry into chromaffin cells is a sufficient stimulus for increasing cellular cyclic AMP production. The possible involvement of a Ca2+/calmodulin-dependent isozyme of adenylate cyclase is discussed.
Keogh
R
R
Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
Marley
P D
PD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000001:Calcimycin; D013779:Tetrodotoxin; D014701:Veratridine; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D004837:Epinephrine