A role for dopamine in growth hormone regulation in the dog.
The role of dopamine (DA) in the secretion of GH in most animal species is still controversial. We examined in the dog the effect on GH release of nomifensine, a drug which activates both noradrenergic and dopaminergic neurotransmission. Nomifensine (0.4-2.8 mg/kg, iv), administered into 12 unanesthetized male and female beagles, induced short-dose-related rises in canine GH (cGH) levels. Blockade of alpha-adrenergic receptors by phentolamine prevented the GH stimulatory effect of 2.8 mg/kg nomifensine, and an iv bolus injection of haloperidol (a neuroleptic which antagonizes both norepinephrine and DA receptor function) given 45 min before was equally effective. Selective blockade of DA receptors by pimozide significantly reduced the GH-releasing effect of nomifensine. In sum, these data indicated that the effect of nomifensine was the consequence of an enhanced noradrenergic and dopaminergic-neurotransmission. Pretreatment with domperidone, a DA receptor blocker unable to cross the blood-brain barrier, failed to modify the GH-releasing effect of nomifensine, suggesting that the DA component subserving the neuroendocrine effect of the drug lies within the blood-brain barrier. Further evidence for a stimulatory role of DA on GH release was the fact that apomorphine, a direct stimulant of DA receptors, induced a rise in cGH levels when administered to dogs pretreated with domperidone. The latter drug was used to prevent emesis and distress due to activation of peripheral DA receptors by apomorphine. However, apomorphine was only active in the dog at doses (250 and 500 microgram/kg, sc) greatly exceeding those active in releasing GH in man, suggesting that the role of DA in cGH regulation is ancillary to that exerted by noradrenergic neurotransmission. In a final study, atropine, a muscarinic cholinergic receptor antagonist, abolished the neuroendocrine effect of nomifensine, a finding which suggests that cholinergic medication plays an important role in cGH regulation.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D004285:Dogs; D004294:Domperidone; D004298:Dopamine / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009627:Nomifensine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology
D001562:Benzimidazoles; D007546:Isoquinolines; D010880:Piperidines; D010868:Pimozide; D009627:Nomifensine; D004294:Domperidone; D001285:Atropine; D013006:Growth Hormone; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D010646:Phentolamine