Mechanisms for pancreatic hypertrophy induced by long-term administration of bethanechol.
Mechanisms for the hypertrophy of rat pancreas induced by long-term administration of bethanechol were investigated. The administration of bethanechol, an acetylcholine receptor agonist, to male Wistar rats for 14 days induced significant increases in the pancreatic weight and contents of protein, amylase and RNA in the pancreas without altering the content of DNA and the incorporation of [3H]thymidine into DNA. Simultaneous administration of atropine with bethanechol suppressed the bethanechol-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-dichlorobenzoyl-amino)-5-(N-3-methoxypropyl-pentylam ino)-5- oxopentanoic acid), an antagonist of cholecystokinin receptors, inhibited pancreatic growth induced by long-term administation of pentagastrin, whereas pancreatic hypertrophy induced by bethanechol was not inhibited by CR1505. These results suggest that long-term administration of bethanechol induces pancreatic hypertrophy through direct activation of muscarinic receptors in the pancreas.
Kato
M
M
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
Kataoka
K
K
Kashima
K
K
Mukainaka
T
T
Kuriyama
K
K
D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D018723:Bethanechol / Q000633:toxicity*; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005755:Gastrins / Q000494:pharmacology; D006984:Hypertrophy / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology*; D010418:Pentagastrin / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D005755:Gastrins; D011949:Receptors, Cholecystokinin; D018723:Bethanechol; C053737:loxiglumide; D001285:Atropine; C036227:gastrin I; D000681:Amylases; D010418:Pentagastrin; D011377:Proglumide; D012844:Sincalide