D-1 dopamine receptors mediate dopamine-induced pancreatic exocrine secretion in anesthetized dogs

Characterization of dopamine (DA) receptor subtypes was examined on the canine exocrine pancreas using selective DA receptor agonists and antagonists in anesthetized dogs. Each drug was injected i.a. in a single bolus fashion. Graded doses of DA (0.01-3 mumol) produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 1 mumol. SCH23390 (3-30 nmol), a selective D-1 DA receptor antagonist, caused a progressive parallel shift to the right in the dose-response curve for DA-induced pancreatic secretion without changes in the maximal response. However, domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize the DA-induced pancreatic exocrine secretion. A Schild analysis of the data indicates that the inhibitory constant value for SCH23390 to inhibit DA-stimulated secretion was 6.9 nmol. In addition, the stimulatory effects of SKF38393 (0.1-10 mumol) and YM435 (0.3-30 nmol), selective D-1 DA receptor agonists, and LY171555 (1-10 mumol), a selective D-2 DA receptor agonist, on pancreatic secretion were demonstrated. The rank order of agonist potency was YM435 > DA > SKF38393 >> LY171555. These results suggest that DA-induced pancreatic exocrine secretion is mediated by activation of D-1 DA receptors.