Cholinergic and histaminergic involvement in the growth hormone releasing effect of an enkephalin analog FK 33-824 in man

Studies were performed in healthy subjects to ascertain the neurotransmitter systems involved in the growth hormone (GH)-releasing effect of the potent enkephalin analog FK 33-824. Concomitant evaluation of prolactin (PRL) secretion was also performed in the same subjects. FK 33-824 at a dose of 0.5 mg IV elicited a clear-cut rise in plasma GH and PRL concentrations with peak levels at 45 min. Blockade of muscarinic cholinergic receptors by atropine (0.5 mg SC) or histaminergic H1 receptors by diphenhydramine (50 mg IV bolus plus 50 mg infusion) completely suppressed the GH release induced by FK 33-824, without significantly altering the PRL rise induced by the peptide. Pretreatment with the alpha-adrenergic antagonist phentolamine (0.5 mg IV/min for 120 min) or the dopamine receptor blocker metoclopramide (10 mg IV) did not alter the GH-releasing effect of FK 33-824. Phentolamine failed to alter the PRL rise induced by FK 33-824, while combined FK 33-824-metoclopramide administration induced a greater PRL increase than FK 33-824 alone. These results indicate that cholinergic and histaminergic H1 receptors play an important role in the GH-release induced by FK 33-824 in man, whereas this action seems to occur independently of catecholaminergic mediation. The same receptors are not involved in the PRL-releasing effect of the peptide.