MODULATION OF PANCREATIC-SECRETION OF INDIVIDUAL DIGESTIVE ENZYMES INOCTREOTIDE (SMS 201-995)-INFUSED RATS

We demonstrated previously that pancreatic secretion of individual enz ymes is specifically regulated (1). In the present study, we investiga ted and defined contributing roles of cholinergic and cholecystokinin tones to the specific regulation of rat pancreatic secretion of digest ive enzymes. Animals were provided with pancreatic, biliary, duodenal, and jugular vein cannulas allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of MK329 or atropi ne sulfate along with SMS 201-995 (SMS). Rats kept in restraint cages were divided into four groups. The first rat group was infused with 5 mu g kg(-1) h(-1) SMS alone; the second group was infused with a mixtu re of SMS and MK329 (5 mu g kg(-1) h(-1):0.5 mg kg(-1) h(-1)); the thi rd group received a mixture of SMS and atropine (5 mu g kg(-1) h(-1)); and rats in the fourth group were administrated a mixture of SMS, MK3 29, and atropine (5 mu g kg(-1) h(-1):0.5 mg kg(-1) h(-1):100 mu g kg( -1) h(-1)). Food, but not water, was denied rats 10 h before the exper iment and throughout the 6-h experimental period. During the experimen t, pancreatic juice was continuously collected every 15 min from each rat, and a 15-mu l aliquot of the pancreatic juice sample was removed for total protein, amylase, lipase, trypsinogen, chymotrypsinogen, and proelastase assays. Pancreatic juice previously collected from a dono r rat was mixed with the fresh bile and the mixture was recirculated i nto the duodenum. The secretory patterns over the 6-h experimental per iod showed that during the first hour of drug infusion, MK329 alone di d not alter the SMS-induced inhibitory process of total protein and am ylase, trypsinogen, and proelastase secretion, and there was no marked change in total protein and enzyme outputs. Adding atropine to SMS di d not alter the secretory pattern during the first hour of drug infusi on, but a significantly greater decrease in protein and enzymes output s occurred. Correlations between paired enzyme outputs greatly increas ed with SMS alone, but some changed when either MK329 or atropine was infused along with SMS. When al drugs were infused together, enzyme ou tputs became strongly correlated. These results suggest that under fas ting conditions, somatostatin and atropine can neutralize basal pancre atic enzyme outputs, leading to a constitutive type of secretion chara cterized by parallel secretion of the digestive enzymes. Furthermore, it is proposed that under basal secretion conditions, acetylcholine an d cholecystokinin reaching the pancreatic acinar cells may act to diss ociate pancreatic secretion of individual digestive enzymes originatin g from heterogeneous secretory granules.