Mechanism of action of apomorphine on rat gastric secretion.
The effects of apomorphine on the volume of gastric secretion and its content of H+, K+, Na+ and Cl- were determined in conscious rats having gastric cannulas. Apomorphine dose-dependently (0.25-0.5 mg/kg s.c.) decreased the volume of gastric secretion, its acid concentration and, at the highest dose, Cl- concentration. However, Na+ and K+ concentrations were unchanged. The alpha 1- and alpha 2-adrenoceptor antagonists prazosin (0.25-0.5 mg/kg i.p.) and yohimbine (5-10 mg/kg i.p.), the beta 1- and beta 2-adrenoceptor antagonist propranolol (5 mg/kg i.p.), the beta 2-adrenoceptor antagonist ICI 118551 (1 mg/kg i.p.) and the dopamine receptor antagonists haloperidol (0.25-2.5 mg/kg i.p.), metoclopramide (2.5-10 mg/kg i.p.) or domperidone (2.5 mg/kg i.p.), administered alone, had little or no effect on the volume, H+, Na+ or Cl- concentrations of gastric secretion. Propranolol prevented the action of apomorphine to reduce the volume of gastric secretion but failed to modify the reductions in H+ and Cl- concentrations. The action of propranolol was mimicked by ICI 118551 but not by the beta 1-adrenoceptor antagonist atenolol. Yohimbine, prazosin or domperidone had little or no effect on the actions of apomorphine. Haloperidol (0.5 mg/kg i.p.) and metoclopramide (10 mg/kg i.p.) antagonised apomorphine's action to reduce H+ and Cl- concentrations but significantly enhanced the action of apomorphine to reduce the volume of gastric secretion. The results suggest that the ability of apomorphine to reduce the volume of gastric secretion is mediated via beta 2-adrenoceptors whilst acid concentration is reduced via an action on neuroleptic sensitive receptors.
Costall
B
B
Naylor
R J
RJ
Tan
C C
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D011412:Propanolamines; D011954:Receptors, Dopamine; D015016:Yohimbine; C026777:ICI 118551; D001262:Atenolol; D001058:Apomorphine; D011224:Prazosin