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The nature of the influence of various polypeptides on gastrin stimulated canine Pavlov pouch secretion Sharp, Fraser Rosslyn

Abstract

The effect of simultaneous continuous infusion of synthetic 15 leucine human gastrin and 4 polypeptides on gastric H⁺ and pepsinogen secretion is studied. The results of 112 five hour secretion tests on 4 Pavlov pouch dogs are reported. The doses of gastrin used were 0.175, 0.35 and 0.7 ug/kg-hr. In 32 control tests the infusion of gastrin alone at the lower doses resulted in stimulation of pepsinogen secretion. The higher dose had no apparent effect. All 3 doses increased the H⁺ output. In 26 tests, simultaneous infusion of synthetic glucagon 5.0 ug/kg-hr and gastrin at the three doses noted above resulted in an inhibition of secretion by about 32% and pepsinogen secretion by about 40%. The characteristics of the inhibition produced conform to a non-competitive pattern. Porcine secretion at a dose of 1.0 ug/kg-hr. inhibited H secretion by about 80 percent at the 3 doses of gastrin used. In these 25 tests the peptic activity of the collected secretion was reduced by 20 percent by secretin infusion. Closer examination of the data however suggests that peptic cell secretion was increased. The pepsinogen probably remained within the gastric gland lumen. The pattern of inhibition of H⁺ secretion had the characteristics of non-competitive inhibition. In 19 tests, a synthetic fragment of the secretin molecule (the N terminal amino acids 12-27) at three doses of 0.5, 1.0 and 2.5 ug/kg-hr. had no effect on gastrin stimulated H⁺ and pepsin secretion. The molecular structural similarities between secretin, glucagon and secretin (12-27) and their observed effects under the conditions of this study suggests the hypothesis: the inhibitory activity on acid secretion of glucagon and secretin reside in the C terminal 11 amino acid sequence. The pepsinogen effect of secretin is dependent on the tertiary molecular structural differences between secretin, secretin (12-27) and glucagon. In ten tests gastric inhibitory polypeptide at a dose of 2.5 ug/kg-hr. inhibited both acid and pepsinogen secretion. The inhibitory effect on H⁺ secretion appeared more marked, in this small number of tests, at a higher background stimulatory dose. This was not so for pepsinogen secretion. All the results reported were subjected to exhaustive statistical evaluation.

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