Abstract

Characterization of dopamine (DA) receptor subtypes was examined on the canine exocrine pancreas using selective DA receptor agonists and antagonists in the isolated and blood-perfused pancreas of 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. High doses of RS-sulpiride (0.3-3 mumol) or haloperidol (1-3 mumol), a mixed D-1/D-2 DA receptor antagonist, also caused a rightward shift in the DA dose-response curve. However, domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize the DA-induced pancreatic exocrine secretion. A modified Schild analysis of the data indicates that SCH23390 is approximately 2 and 3 orders of magnitude more potent than RS-sulpiride and haloperidol, respectively. In addition, the stimulatory effects of DA (0.01-3 mumol), SKF38393 (0.1-10 mumol, a selective D-1 DA receptor agonist) and LY171555 (1-10 mumol, a selective D-2 DA receptor agonist) on pancreatic secretion were demonstrated. The rank order of agonist potency was DA greater than SKF38393 greater than LY171555. The secretory response to LY171555 was inhibited completely by pretreatment with SCH23390 (30 nmol).(ABSTRACT TRUNCATED AT 250 WORDS)