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

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Abstract
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-iduced 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-adrenoceptors are unlikely to be involved in the mechanism of action of metoclopramide. Although there is some evidence that peripheral dopamine receptors may be involved, the fact that metoclopramide significantly increased gastric emptying in the absence of 6,7-ADTN suggests that its dopamine receptor antagonist properties may contribute only in part towards its mechanism of action.