Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): possible involvement of an Na+/Ca2+ exchange mechanism.
The effect of pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated the efflux of 45Ca2+ from the cells in a concentration dependent manner (10(-9)-10(-7)M). This effect was inhibited by its potent receptor antagonist PACAP6-38. PACAP1-38 increased the formation of [3H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45Ca2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP1-38-induced 45Ca2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45Ca2+ from the cells. The increases in 45Ca2+ efflux induced by PACAP1-38 and forskolin were reduced by deprivation of extracellular Na+ and the Na+/Ca2+ exchange inhibitor amiloride. In addition, PACAP1-38 stimulated 22Na+ influx into the cells, and this action was inhibited by amiloride. These results suggest that PACAP1-38 stimulates an Na+/Ca2+ exchange mechanism through activation of adenylate cyclase in cultured bovine adrenal chromaffin cells.
Houchi
H
H
Department of Pharmacology, School of Medicine, University of Tokushima, Japan.
Okuno
M
M
Kitamura
K
K
Minakuchi
K
K
Ishimura
Y
Y
Ohuchi
T
T
Oka
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019831:Sodium-Calcium Exchanger; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D007295:Inositol Phosphates; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019831:Sodium-Calcium Exchanger; D005576:Colforsin; D000584:Amiloride; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine