Effects of SMS 201-995 on basal and stimulated pancreatic secretion in rats.
Somatostatin (SRIF) is a potent inhibitor of most gastrointestinal and pancreatic functions. Recently, we showed that SRIF given either iv or intraduodenally (id) strongly inhibited stimulated pancreatic secretion induced by pancreatic juice diversion (PJD) from the duodenum. In this study we evaluate the effects of iv and id infusion of a long acting analog of SRIF, SMS 201-995 (SMS), on pancreatic secretion during basal conditions (pancreatic juice returned) and PJD. Conscious rats prepared with bile, pancreatic, duodenal, and jugular cannulae were studied 3-8 days postoperatively. Protein and fluid outputs were evaluated, and plasma cholecystokinin (CCK) was measured by bioassay. iv SMS infusion (5 micrograms kg-1 h-1) inhibited basal pancreatic protein and fluid secretion by 84 and 64%, respectively. Addition of atropine (500 micrograms kg-1 h-1 ip) did not cause further inhibition. During PJD, SMS iv from 0.005-1.28 micrograms kg-1 h-1 for 3 h caused a dose-dependent inhibition with maximal 90% and 75% reductions of protein and fluid, respectively, at 1.28 micrograms SMS. Plasma CCK was also reduced by 83% from 3.01 +/- 1.15 to 0.51 +/- 0.22 pM. SMS, id at 1.7 micrograms kg-1 h-1 for 1.5 h before and 2 h after PJD, caused inhibition of basal secretion by 25% and that induced by PJD by 60%. Plasma CCK, measured 1.5 h after diversion, increased from 1.55 +/- 0.06 to 5.9 +/- 1.14 pM in the presence of SMS. Intravenous SMS was 20 times more potent than SRIF in inhibiting pancreatic protein and volume secretion stimulated by PJD. Iv SMS inhibited basal and stimulated fluid and protein pancreatic secretion as well as plasma CCK levels. SMS was also effective when given id in inhibiting fluid and protein pancreatic secretion, but id SMS increased plasma CCK levels. This effect on plasma CCK may be due to the inhibition of hormonal inhibitors of CCK release.
Guan
D
D
Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Québec, Canada.
Maouyo
D
D
Sarfati
P
P
Morisset
J
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood; D007700:Kinetics; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D001285:Atropine; D002766:Cholecystokinin; D015282:Octreotide