MECHANISMS FOR PANCREATIC HYPERTROPHY INDUCED BY LONG-TERM ADMINISTRATION OF BETHANECHOL

Mechanisms for the hypertrophy of rat pancreas induced by long-term ad ministration of bethanechol were investigated. The administration of b ethanechol, an acetylcholine receptor agonist, to male Wistar rats for 14 days induced significant increases in the pancreatic weight and co ntents of protein, amylase and RNA in the pancreas without altering th e content of DNA and the incorporation of [H-3]thymidine into DNA. Sim ultaneous administration of atropine with bethanechol suppressed the b ethanechol-induced pancreatic hypertrophy. Long-term administration of other acetylcholine receptor agonists also showed similar effects as produced by bethanechol. CR1505 (loxiglumide; D,L-4-(3,4-dichlorobenzo yl-amino)-5-(N-3 lamino)-5-oxopentanoic acid), an antagonist of cholec ystokinin receptors, inhibited pancreatic growth induced by long-term administration of pentagastrin, whereas pancreatic hypertrophy induced by bethanechol was not inhibited by CR1505. These results suggest tha t long-term administration of bethanechol induces pancreatic hypertrop hy through direct activation of muscarinic receptors in the pancreas.