The relative blood flow distribution within the small intestine of anesthetized cats was investigated during resting conditions and when superior mesenteric blood flow was increased 15--85% by the intravenous infusion of secretin, cholecystokinin (CCK), or isoproterenol. Radioactive microspheres of 15 mum diameter were injected into the superior mesenteric artery and shortly thereafter intestinal segments were removed and dissected into mucosal, submucosal, and muscularis fractions. Tissue weights and the radioactivity of each were determined. During secretin-induced mesenteric vasodilatation there was a significant redistribution of blood away from the jejunal mucosa to the submucosa. During CCK and isoproterenol infusions there were significant increases in mucosal and decreases in submucosal blood flow. No significant changes were observed in muscularis flow. There was no apparent relationship between the percent increase in SMBF and the relative blood flow distribution changes observed. The results indicate that while secretin, CCK, and isoproterenol increase superior mesenteric blood flow, they also affect blood flow distribution within the mucosa and submucosa.
1 The performance of oxprenolol and metoprolol Oros systems has been evaluated in the dog. One study compared in vivo and in vitro release from both systems over 2-14 h. The other compared the systemic availabilities of both drugs after 3 h infusion at a constant rate into the cephalic and hepatic portal veins, and into the lumen of the duodenum and colon. 2 In the in vivo release studies, Oros systems were recovered throughout the gut from the stomach to the colon. The amounts of drug remaining in the systems corresponded closely to those measured in a parallel in vitro release experiment. In vitro testing is thus a reliable indicator of in vivo system performance. 3 In the absorption studies, both metoprolol and oxprenolol were shown to be subject to substantial first-pass metabolism. Additionally, for metoprolol the data indicated a significant loss during transport from the gut lumen into the portal circulation. For both drugs the availability from the colon was equal to that from the duodenum. 4 These results provide some justification for the development of oral dosage forms with extended durations of release even for drugs which undergo significant first-pass metabolism.
Effects of OP-CCK, gastrin, and secretin were studied on isometric tension development in strips of cat gallbladder. Effective molar concentrations were 2.2 X 10(-10) to 5.3 X 10(-9) for OP-CCK, and 1.13 X 10(-7) to 1.5 X 10(-6) for gastrin. The maximal response to gastrin averaged 66% the maximal response to OP-CCK and effects were not blocked by atropine. Secretin was weakly stimulatory or ineffective by itself. Prior addition of submaximal doses of gastrin shifted the dose-response curve of OP-CCK to the right, but neither the slope nor the calculated maximal response (CMR) was significantly changed. This suggests that gastrin and OP-CCK compete for a common receptor on cat gallbladder. On the other hand, a background dose of secretin shifted the dose-response curves for both OP-CCK and gastrin to the left and increased the slopes significantly with increase in the respective CMRs. The combined action of OP-CCK (or gastrin) and secretin are supra-additive. These experiments suggest that OP-CCK and gastrin act at a common receptor site which is different from the secretin-receptor site.
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