A B S T R A C T The nature and extent of growth hormone-release inhibiting hormone (GH-RIH, somatostatin) -induced inhibition of pancreatic secretion of bicarbonate and protein, an index of enzyme secretion, were studied by administration of exogenous secretin or cholecystokinin (CCK) and of a number of stimulants for endogenous release of these hormones in fasted pancreatic fistula dogs with and without an infusion of GH-RIH.The results of this study show that GH-RIH inhibits the pancreatic fluid and bicarbonate secretion induced by both duodenal acidification and exogenous secretin. The kinetic analysis shows that the interaction between GH-RIH and secretin affecting pancreatic bicarbonate secretion possesses the characteristics of competitive inhibition. GH-RIH does not change the pancreatic protein response to exogenous CCK, but profoundly inhibits pancreatic response to a variety of the endogenous stimulants of CCK release, including duodenal perfusion of sodium oleate, amino acid mixture, or feeding of a peptone meal. We conclude that GH-RIH is a very potent inhibitor of the endogenous release of CCK from the intestinal mucosa and inhibits competitively the action of secretin but not CCK on the exocrine pancreatic secretion.

SUMMARY1. Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to i.v. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution.2. VIP and secretin infused i.v. in cats produced superimposable pancreatic dose-response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17 % of that to secretin (Konturek, Thor, Dembinski & Krol, 1975). It is concluded that VIP in cats is a secretin-like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion.3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin-induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas.4. Caerulein, an analogue of CCK-P,, infused i.v. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dosedependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone.5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose-response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be S. J. KONTUREK AND OTHERS accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK-P. or to the vago-vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion.

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This investigation was designed to assess the effects of oral administration of melatonin (10 mg) and tryptophan (Trp) (500 mg) on fasting and postprandial plasma levels of melatonin, gastrin, ghrelin, leptin and insulin in 10 healthy controls and in age-matched patients with liver cirrhosis (LC) and portal hypertension. Fasting plasma melatonin levels in LC patients were about five times higher (102 +/- 15 pg/mL) than in healthy controls (22 +/- 3 pg/mL). These levels significantly increased postprandially in LC patients, but significantly less so in controls. Treatment with melatonin or L-Trp resulted in a further significant rise in plasma melatonin, both under fasting and postprandial conditions, particularly in LC patients. Moreover, plasma gastrin, ghrelin, leptin and insulin levels under fasting and postprandial conditions were significantly higher in LC subjects than in healthy controls and they further rose significantly after oral application of melatonin or Trp. This study shows that: (a) patients with LC and portal hypertension exhibit significantly higher fasting and postprandial plasma melatonin levels than healthy subjects; (b) plasma ghrelin, both in LC and healthy controls reach the highest values under fasting conditions, but decline postprandially, especially after oral application of melatonin or Trp; and (c) plasma melatonin, gastrin, ghrelin and insulin levels are altered significantly in LC patients with portal hypertension compared with that in healthy controls possibly due to their portal systemic shunting and decreased liver degradation.

Somatostatin, a growth hormone-release inhibiting hormone, has been found to be a powerful inhibitor of gastric and pancreatic secretion as well as of hormone release in the digestive system. This study was undertaken to determine the influence of somatostatin on the myoelectrical activity pattern of the small bowel. Three conscious dogs were prepared with electrodes spaced 25 cm apart along the entire small intestine. Intravenous infusions of somatostatin were administered in various doses (0.6--5.0 microgram/kg.h) while spike activity and slow waves were recorded under fasting conditions, after a meat meal, or during intravenous infusion of gastrin, caerulein, or insulin. Somatostatin at a dose of 0.6 microgram/kg.h almost doubled the frequency of the interdigestive myoelectric complex. Somatostatin in fed dogs caused a dose-dependent decrease of the normal fed spike activity, and at higher doses it induced a pattern like that seen in fasting animals. The slow-wave frequency in both fasted and fed conditions was not changed significantly. We conclude that somatostatin given under basal conditions increases the frequency of the interdigestive complex and, when administered after feeding, converts the fed-type pattern to the fasted-type pattern. It may therefore play a promoting role in initiating the interdigestive myoelectric complex.