The role of alpha-adrenergic mechanisms within the area postrema in dopamine-induced emesis.
Intracerebroventricular injection of dopamine (0.5-4.0 mg) produced dose-dependent and short-lasting emesis (1-8 min) in cats, which was abolished after ablation of the area postrema. Relatively selective alpha 2-adrenoceptor antagonists (yohimbine and idazoxan) and a mixed alpha 1- and alpha 2-adrenoceptor antagonist (tolazoline), but not a non-selective alpha 1-adrenoceptor antagonist (prazosin), injected intracerebroventricularly inhibited the emesis induced by intracerebroventricular dopamine. However, dopamine receptor antagonists (chlorpromazine, droperidol, spiperone, domperidone, triflupromazine, sulpiride and metoclopramide), an antimuscarinic drug (atropine), a ganglionic blocking agent (mecamylamine), an opioid receptor antagonist (naloxone) and a 5-HT receptor antagonist (methysergide), all injected intracerebroventricularly, had no significant effect on emesis evoked by intracerebroventricular dopamine. The emetic response to intracerebroventricular dopamine was attenuated in cats pretreated with intracerebroventricular reserpine, 6-hydroxydopamine, alpha-methyl-p-tyrosine and hemicholinium-3. It is postulated that dopamine-induced emesis is mediated through the release of noradrenaline acting at alpha 2-adrenoceptors and that it depends on the integrity of monoaminergic and possibly cholinergic structures within the area postrema. It appears, therefore, that the emetic effect of intracerebroventricular dopamine is mediated by adrenergic rather than dopaminergic mechanisms in the area postrema, at least in the cat.
Jovanović-Mićić
D
D
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Samardzić
R
R
Beleslin
D B
DB
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002415:Cats; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000378:metabolism; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000494:pharmacology; D019329:Idazoxan; D007276:Injections, Intraventricular; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008781:Methyltyrosines / Q000008:administration & dosage / Q000494:pharmacology; D008784:Methysergide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology; D014043:Tolazoline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019805:alpha-Methyltyrosine
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018492:Dopamine Antagonists; D008781:Methyltyrosines; D015016:Yohimbine; D006426:Hemicholinium 3; D009270:Naloxone; D019805:alpha-Methyltyrosine; D008464:Mecamylamine; D001285:Atropine; D012110:Reserpine; D016627:Oxidopamine; D014043:Tolazoline; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D011224:Prazosin; D008784:Methysergide; D019329:Idazoxan