Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells.
Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. To study the loci where nicotine might exert its effect, we examined interactions between nicotine and rat pancreatic acini. When pancreatic acini were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were increased in time-and dose-dependent manners, and the t1/2 for dissociation of [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was 33% of the association at 37 degrees C. Unlabeled nicotine had no significant effect on the accumulation of [3H]nicotine. In addition, surface-bound [3H]nicotine was not detected when acini were washed in a low-pH solution or when they were trypsinized. These results suggest that the accumulation of nicotine may be a biological phenomenon and that [3H]nicotine does not bind to surface receptors of acinar cells, but accumulates intracellularly. The addition of verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10 mM) significantly increased the accumulation of [3H]nicotine. Carbachol and cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose-dependent manner. Taken together, the increasing effects of carbachol and cholecystokinin on the accumulation of nicotine may explain, at least in part, the mechanisms involved in the multiplicative effects of the combination of two risk factors, smoking habit and high-fat or high-protein diets, on human pancreatic diseases.
Doi
R
R
First Department of Surgery, Kyoto University, Japan.
Chowdhury
P
P
Nishikawa
M
M
Takaori
K
K
Inoue
K
K
Imamura
M
M
Rayford
P L
PL
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
D014316:Tritium; D009538:Nicotine; D002217:Carbachol; D002766:Cholecystokinin; D014700:Verapamil