The role of dopamine (D2), alpha and beta-adrenoceptor receptors in the decrease in gastrointestinal transit induced by dopamine and dopamine-related drugs in the rat.

Abstract

This study analyses the effects of dopamine receptor agonists and antagonists on rat gastrointestinal transit (GIT) in an attempt to identify the mechanisms involved. Dopamine (DA), apomorphine, quinpirole, bromocriptine and fenoldopam were given by subcutaneous (s.c.), intrathecal (i.t.), intracisternal (i.c.) and/or intraperitoneal (i.p.) routes. In general, DA (200 micrograms, i.t.), apomorphine (3, 5 and 10 mg/kg, s.c.; or 10, 30 and 100 micrograms, i.t.), and bromocriptine (1, 5 and 10 mg/kg, s.c.) elicited decreases in gastrointestinal transit which were significantly antagonized by the D2 receptor antagonists domperidone or alizapride (both 5 mg/kg, s.c.), but remained unaffected by the D1 receptor antagonist SCH 23390 (5 mg/kg, s.c.). Similarly, DA (50, 100 and 200 micrograms, i.c.) and apomorphine (12 and 50 micrograms; i.c.) produced dose-dependent decreases in gastrointestinal transit amenable to blockade by the classical DA receptor antagonist haloperidol (10 micrograms, i.c.). The responses to apomorphine (3, 5 and 10 mg/kg, s.c.) were unaltered by 6-hydroxydopamine (100 mg/kg, i.p.)-induced sympathectomy but were antagonized by both propranolol (1 mg/kg, s.c.) and phentolamine (5 mg/kg, s.c.). Significantly, after bilateral (cervical) vagotomy, gastrointestinal transit was markedly reduced, but apomorphine (5 mg/kg, s.c.) apparently further reduced gastrointestinal transit. The D1 agonists fenoldopam (5, 10 and 20 mg/kg, s.c.) significantly reduced GIT. Fenoldopam-induced antitransit effects were markedly modified by the D1 receptor antagonist, SCH 23390 (5 mg/kg, s.c.); only the response induced by 5 mg/kg of fenoldopam was apparently antagonized by SCH 23390. The mixed D2 and D3 receptor agonist quinpirole (4 and 8 mg/kg, s.c.; or 8 mg/kg, i.p.; 200 micrograms, i.t.) did mimic DA eliciting significant reductions in gastrointestinal transit which, however, were not antagonized by domperidone (5 mg/kg, s.c.). Taken together, the present results support the contention that the decrease in rat gastrointestinal transit induced by DA and apomorphine may be mediated by an interaction with central and/or peripheral D2 receptors. The presence of dopamine receptors (D2) in the alimentary canal are strengthened by antitransit effect of fenoldopam and bromocriptine in the gastrointestinal tract.