Abstract

The effects of YM435, a novel dopamine (DA) D 1 receptor agonist, on pancreatic exocrine secretion were investigated in anesthetized dogs. Each drug was injected i.a. as a single bolus. Graded doses of YM435 (0.3–30 nmol) produced dose-dependent increases in the rate of secretion of pancreatic juice, with a maximum effect at approximately 10 nmol, and with a high concentration of bicarbonate and low concentration of protein. SCH23390 (3–30 nmol), a selective D 1 receptor antagonist, caused a progressive parallel shift to the right of the dose-response curve for YM435-stimulated pancreatic secretion without changing the maximum response. Schild analysis of the data indicated that the inhibitory constant (K i) value was 2.9 nmol, and that SCH23390 inhibited YM435-stimulated pancreatic secretion in a competitive manner. Both DA (0.01–3 μmol) and SKF38393 (0.3–30 μmol), a selective D 1 receptor agonist, also increased the secretory rate and bicarbonate concentration, and decreased the protein concentration to the same extent as YM435. These results suggest that YM435 is a potent stimulant of pancreatic exocrine secretion by acting on DA D 1 receptors of the pancreas in dogs.

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