ROLE OF DOPAMINE AND α‐ADRENORECEPTORS IN THE CONTROL OF GASTRIC EMPTYING IN THE RAT: POSSIBLE INVOLVEMENT IN THE MECHANISM OF ACTION OF METOCLOPRAMIDE

The object of the study was to investigate the effects of dopamine receptor and alpha-adrenoreceptor agonists and antagonists on the gastric emptying of a liquid test meal in conscious rats and the possible involvement of these receptors in the mechanism of action of metoclopramide. The gastric emptying of a liquid test meal in conscious chronic gastric fistula rats was delayed following subcutaneous administration of either 6,7-ADTN (1-50 mg/kg) or clonidine (0.05-1 mg/kg). Phenylephrine (0.2-10 mg/kg s.c.) had no effect on gastric emptying, suggesting that dopamine and alpha 2-, but not alpha 1-adrenoreceptors may be involved in the control of gastric emptying in the rat. Phentolamine (0.2-5 mg/kg s.c.) and prazosin (0.1-0.5 mg/kg s.c.) potentiated the delay in gastric emptying induced by 6,7-ADTN, whilst yohimbine (1-5 mg/kg s.c.) and prazosin (0.1-0.5 mg/kg s.c.) reversed the delay in emptying induced by clonidine. All three alpha-adrenoreceptor antagonists also delayed gastric emptying in the absence of agonist. Propranolol (0.2-5 mg/kg s.c.) had no effect on either normal or delayed gastric emptying. Both metoclopramide (1-10 mg/kg s.c.) and haloperidol (0.02-0.5 mg/kg s.c.) reversed the 6,7-ADTN-induced delayed emptying but not the clonidine-induced delayed emptying. In addition, metoclopramide (5-10 mg/kg s.c.), but not haloperidol, increased gastric emptying in the absence of agonist. In conclusion, these results show that dopamine and alpha-adrenoreceptors may be involved in the control of gastric emptying in the rat. However, it would appear that alpha 2-adrenoreceptors are unlikely to be involved in the mechanism of action of metoclopramide.(ABSTRACT TRUNCATED AT 250 WORDS)