Phorbol ester facilitates 45Ca accumulation and catecholamine secretion by nicotine and excess K+ but not by muscarine in rat adrenal medulla.
Several investigators have shown that tumour promoter phorbol esters mimic the effects of endogenous diacylglycerol to activate a second messenger, protein kinase C. These phorbol esters have proved to be valuable tools for exploring the role of protein kinase C in many cellular functions. We demonstrate here that secretion of catecholamines evoked from the rat adrenal gland by stimulation of splanchnic nerves, excess potassium (K+) and nicotine is facilitated by phorbol 12,13-dibutyrate. An inhibitor of protein kinase C, polymixin B, produced concentration-dependent inhibition of the evoked secretion, and the effect was reversed by the phorbol ester. Furthermore, we show that an increase in the accumulation of radioactively labelled calcium (45Ca) obtained in the adrenal medulla after stimulation with nicotinic agonists and excess K+ is further enhanced by phorbol ester. Muscarine-evoked secretion of catecholamines, which depends on mobilization of intracellularly bound Ca2+, was not associated with an increase in 45Ca2+ uptake, and phorbol ester did not facilitate either catecholamine secretion or 45Ca2+ accumulation. We suggest that protein kinase C is involved in the exocytotic secretion of catecholamines by regulating the influx of Ca2+ through voltage-sensitive and nicotine receptor-linked Ca2+ channels of rat chromaffin cells.
A R
AR
Wakade
R K
RK
Malhotra
T D
TD
Wakade
D000313:Adrenal Medulla / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009116:Muscarine / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects
D002395:Catecholamines; D010703:Phorbol Esters; D011978:Receptors, Nicotinic; D009538:Nicotine; D009116:Muscarine; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium