Activation of the cholinergic system and growth hormone release in the dog: functional interactions with other neurotransmitters.
In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Diphenhydramine and meclastine, two antagonists of histamine (H) H1 receptors completely suppressed the GH-releasing effect of eserine, while cimetidine, an H2 receptor antagonist, only blunted and delayed it. Two long-lasting serotonin (5-HT) receptor antagonists, metergoline and pizotifen, partially or completely suppressed, respectively, GH release evoked by eserine, whereas fenfluramine, a releaser of neuronal stores of 5-HT and hence a functional activator of 5-HT neurotransmission, was ineffective in this context. Pimozide, a long-acting dopamine receptor antagonist, abolished the effect of eserine, whereas domperidone, which has the same pharmacological properties but does not cross the blood brain barrier, failed to do so. Finally, phentolamine, an antagonist of alpha-adrenoceptors, and propranolol, a beta-adrenergic antagonist, were completely ineffective in preventing the rise in plasma cGH levels induced by eserine, as was naloxone, an antagonist of opiate receptors. All these data demonstrate that, although cholinergic mechanisms are involved in the mechanism(s) underlying cGH release, the final common pathway for GH secretion is not cholinergic. Preservation of dopaminergic and H1 neurotransmission, probably within the blood barrier, is needed to allow the neuroendocrine transduction of cholinergic inputs, whereas the role of 5-HT neurotransmission remains uncertain.
Betti
R
R
Casanueva
F F
FF
Cella
S G
SG
Müller
E E
EE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D002974:Clemastine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D010868:Pimozide / Q000494:pharmacology; D010918:Pizotyline / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011863:Radioimmunoassay; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D011950:Receptors, Cholinergic; D010918:Pizotyline; D008711:Metergoline; D010868:Pimozide; D005277:Fenfluramine; D009270:Naloxone; D004294:Domperidone; D002927:Cimetidine; D004155:Diphenhydramine; D013006:Growth Hormone; D002974:Clemastine; D010830:Physostigmine; D011433:Propranolol; D010646:Phentolamine