Nicotine stimulates pepsinogen secretion from guinea pig gastric chief cells in monolayer culture.
We evaluated the effects of nicotine on pepsinogen secretion in vitro, using a monolayer culture system of guinea pig gastric chief cells. Pepsinogen secretion was increased by above 5 mM nicotine in a dose-dependent manner, as was the elevation of intracellular free calcium concentration ([Ca2+]i). The pepsinogen secretion stimulated by 10 mM nicotine was inhibited by above 1 mM d-tubocurarine, a nicotinic receptor antagonist, but not by same concentrations of scopolamine hydrobromide monohydrate or pirenzepine, a muscarinic receptor antagonist. The elevation of [Ca2+]i induced by 5 mM nicotine was also reduced by 10 mM d-tubocurarine, but not by 10 mM pirenzepine. A calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), at the concentration of 10(-6) M and a myosin light-chain kinase inhibitor, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), at concentrations above 10(-7) M also significantly blocked 10 mM nicotine-induced pepsinogen secretion. These finding indicate that nicotine directly stimulates pepsinogen secretion probably via nicotinic receptors on the gastric chief cells, and that the Ca(2+)-mediated messenger system, including calmodulin and myosin light-chain kinase, is involved in this event.
Okayama
N
N
First Department of Internal Medicine, Nagoya City University Medical School, Japan.
Itoh
M
M
Joh
T
T
Miyamoto
T
T
Takeuchi
T
T
Kato
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002470:Cell Survival; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009538:Nicotine / Q000494:pharmacology*; D010435:Pepsinogens / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D001381:Azepines; D002038:Bungarotoxins; D002147:Calmodulin; D010435:Pepsinogens; D013449:Sulfonamides; C056218:ML 9; D010890:Pirenzepine; C017967:W 7; D009538:Nicotine; D012601:Scopolamine; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D014403:Tubocurarine