The response of pancreatic polypeptide (PP) to testmeal (5 ml/kg) and intraduodenal acid (4 mEq HCl/5min) and its reaction to somatostatin (3.5 microgram/kg/h following bolus injection of 3.5 microgram/kg) was studied in dogs with chronic duodenal and gastric fistulae. In addition the influence of atropin (0.5 mg/kg/h) on acid-induced PP response was examined. PP was measured by radioimmunoassay pancreatic secretion by determinating volume, bicarbonate, protein, and enzyme in duodenal contents and pancreatic juice. Plasma PP increased significantly following intraduodenal application of testmeal and hydrochloric acid. Its release was completely suppressed by SST. Furthermore, PP response to intraduodenal acid was blocked by atropin. Exocrine pancreatic secretion of bicarbonate and protein was inhibited by somatostatin as well as atropin. Since PP was released following administration of testmeal and acid, both potent stimulators of pancreatotropic duodenal hormones, it may play an important role in the control of the entero-pancreatic axis. The effect of atropin indicates a cholinergic nervous component of PP release.
SUMMARY Graded doses of 0 1, 0*3, 0 9, and 2-7 clinical units/kg/h of pure synthetic secretin were infused over 60 minute periods in six healthy volunteers. Duodenal bicarbonate output and pH were recorded and plasma secretin and motilin levels were measured by radioimmunoassay. During the infusions plasma motilin fell in a dose dependent manner to a nadir of 35 %. This fall was linearly correlated with pancreatic bicarbonate output, whereas a non-linear correlation was observed between plasma motilin and both plasma secretin level and duodenal pH. It is suggested that plasma motilin levels are decreased by secretin-induced pancreatic bicarbonate juice flow. This may be important for the control of motilin secretion initiated by duodenal acidification and the concomitant delay in gastric emptying.Motilin, a recently discovered hormonal peptide from the small intestine (Brown et al., 1971), has been shown to increase lower oesophageal sphincter pressure and to delay gastric emptying in man (Ruppin et al., 1975; Rosch et al., 1976).So far, no physiological regulation of motilin secretion has been ascertained. In the dog it has been reported that serum motilin levels are raised by strong duodenal alkalinisation (Dryburgh and Brown, 1975). We have shown recently that, in man, motilin is released by duodenal acidification and after intraduodenal instillation of tris buffer (pH 102) motilin fell . As, however, a duodenal pH of 10-2 is unlikely to be achieved under normal conditions, the significance of this finding is uncertain. The present study was designed to assess the effect on motilin release of secretin. This peptide initiates a physiological alkalinisation of the duodenum by stimulating endogenous alkaline pancreatic juice flow (Jorpes and Mutt, 1961). MethodsSix healthy volunteer men (aged 23-42 years) were "Address for reprint requests:
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