Modulatory effect of 4 beta-phorbol 12-myristate 13-acetate (PMA) on carbachol-induced Ca2+ mobilization in rat parotid acinar cells.
Treatment of rat parotid acinar cells with 4 beta-phorbol 12-myristate 13-acetate (PMA) significantly inhibited an increase in cytosolic free Ca2+ concentration ([Ca2+]i) induced by carbachol (CCh), a muscarinic agonist. The CCh-induced increase in [Ca2+]i was also inhibited by another active phorbol ester, 4 beta-phorbol 12,13-dibutyrate, but not by 4 alpha-phorbol 12,13-didecanoate, which does not activate protein kinase C. The treatment with PMA had no effect on increases in [Ca2+]i evoked by ionomycin and thapsigargin, which do not stimulate phosphoinositide hydrolysis. In contrast, an increase in [Ca2+]i induced by NaF, a direct activator of GTP-binding proteins, was delayed in the presence of PMA. The formation of inositol phosphates in response to CCh was suppressed significantly by PMA treatment. In radioligand binding assays, PMA did not directly interfere with the specific binding of [3H]quinuclidinyl benzilate ([3H]QNB), a muscarinic antagonist, to plasma membranes. Furthermore, the [3H]QNB binding to plasma membranes prepared from the PMA-pretreated cells was not different from that to the control membranes. These results indicate that PMA attenuated the CCh-induced increase in [Ca2+]i through inhibition of phosphoinositide hydrolysis. Activation of protein kinase C may play a role in negative-feedback control of the muscarinic pathway in rat parotid acinar cells.
Tojyo
Y
Y
Department of Dental Pharmacology, School of Dentistry, Higashi Nippon Gakuen University, Hokkaido, Japan.
Tanimura
A
A
Matsumoto
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007295:Inositol Phosphates / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D010306:Parotid Gland / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019284:Thapsigargin
D007295:Inositol Phosphates; D013729:Terpenes; D015759:Ionomycin; D019284:Thapsigargin; D002217:Carbachol; D012969:Sodium Fluoride; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium