In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h; respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 ml for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM (n = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)
We investigated the existence of an enterogastrone in rats induced by duodenal administration of oleic acid. Acid secretion by the luminally perfused stomach was stimulated in anesthetized rats by intravenous infusion of 0.3 micrograms.kg-1.h-1 pentagastrin. Intraduodenal administration of 3 mmol of oleic acid produced a profound inhibition (94%) of pentagastrin-stimulated acid output in 10 rats (P less than 0.01). Of several peptides in plasma including secretin, neurotensin, somatostatin, and peptide YY, only secretin was found to increase significantly (P less than 0.001). A similar degree of inhibition of acid output (93%) was caused by porcine secretin, 5.6 pmol.kg-1.h-1, given intravenously to mimic the plasma level of secretin produced by oleic acid infusion. The inhibitory effect of oleic acid on the acid secretion was completely reversed by intravenous injection of a rabbit antisecretin serum but not by a normal rabbit serum. These observations strongly suggest that the inhibition was mediated via circulating secretin. The inhibition produced by either oleic acid or secretin was completely blocked by indomethacin. The blocking action was completely reversed by intravenous administration of 48 micrograms.kg-1.h-1 prostaglandin E2. We conclude that endogenous secretin is a major enterogastrone released by oleic acid in anesthetized rats and that the inhibitory action of secretin requires endogenous prostaglandins.
Electroacupuncture (EAP) was shown to inhibit basal gastric acid secretion in dogs and sham feeding-stimulated acid secretion in humans. However, its effect on a meal-stimulated acid secretion in dogs and the mechanisms involved remain unclear. In five dogs prepared with gastric cannulas, gastric acid secretion was determined by a dye-dilution technique for 60 min after intragastric administration of 200 ml of 4% mixed amino acid meal in six different experiments: study 1, no acupuncture; study 2, sham acupuncture (SAP); study 3, EAP; study 4, EAP plus naloxone; study 5, naloxone alone; and study 6, intravenous infusion of somatostatin (SS) and vasoactive intestinal peptide (VIP) at doses of 0.5 and 1.0 micrograms.kg-1.h-1, respectively. EAP was performed on three different points including Pishu, ZusanLi, and Neiguan. Biphasic electrical pulse (25-100 Hz, 12-16 mA) was applied continuously via needles for 75 min starting 15 min before meal. SAP on nonacupoints in hind- and forelegs was performed with the same electrical pulse. Plasma SS, VIP, beta-endorphin, and gastrin were determined by specific radioimmunoassays. EAP significantly inhibited acid secretion (75%; P < 0.01), which coincided with significant increases in plasma SS, VIP, and beta-endorphin and a significant decrease in plasma gastrin. Naloxone completely reversed EAP-induced inhibition of acid secretion and changes in plasma concentration of peptides. SAP also significantly suppressed acid output (30%; P < 0.05), with a modest but significant increase in plasma beta-endorphin. However, the inhibition by EAP on the acid output was significantly greater than that by SAP (P < 0.01). Furthermore, exogenous SS (0.5 microgram.kg-1.h-1) significantly inhibited acid output (78%), whereas VIP failed to inhibit gastric acid secretion. We conclude that, in dogs, EAP significantly inhibits meal-stimulated acid secretion. This acid inhibition is mediated by the release of beta-endorphin and somatostatin, and an endogenous opiate or opiates appear to play an important role in the release of SS, VIP, and beta-endorphin.
Secretin has been known to inhibit gastric acid secretion in several species. However, the physiological role of secretin on the postprandial acid output and gastric emptying in an intact stomach remains controversial. In the present study, we reinvestigated the role of secretin in physiological dose range and endogenous secretin on gastric acid secretion and emptying in the stomach without influencing intragastric luminal pH in dogs. In seven conscious dogs with gastric cannulas, a 4% amino acid meal was administered intragastrically, and three different doses of secretin and an antisecretin serum were infused intravenously in each dog on separate days. Gastric emptying and net acid output were measured using a dye dilution technique, and plasma secretin and gastrin were determined by specific radioimmunoassays. After the meal, gastric emptying was exponential: acid output peaked at 25 min, and plasma concentrations of gastrin and secretin peaked at 15 and 60 min, respectively. Intravenous infusion of secretin at 1.25, 2.5, and 5.0 pmol.kg-1.h-1 dose dependently increased plasma levels of the peptide and suppressed postprandial plasma gastrin response and gastric acid output and emptying of the meal. Immunoneutralization of circulating secretin with a rabbit antisecretin serum abolished the postprandial rise of plasma secretin and significantly increased plasma gastrin, and augmented gastric emptying as well as acid output. It is concluded that, in dogs, secretin plays a physiological role in the regulation of gastric emptying and acid output after a liquid amino acid meal and that these effects may be mediated in part by suppression of the release of gastrin.
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