Effect of pindolol on the L-5-HTP-induced increase in plasma prolactin and cortisol concentrations in man.
Previous studies with direct-acting serotonin (5-HT) agonists and antagonists have demonstrated that stimulation of 5-HT1A, 5-HT1C and 5-HT2 receptors may promote cortisol and prolactin (PRL) secretion in man. There is also evidence that 5-HT1C/2 receptor stimulation contributes to the cortisol and PRL responses following administration of the 5-HT precursor, L-5-hydroxytryptophan (L-5-HTP), in man. To clarify the possible contribution of 5-HT1A receptor stimulation to the ability of L-5-HTP to stimulate cortisol and PRL secretion in man, the effect of pindolol, a beta adrenoceptor antagonist that is also a 5-HT1A partial agonist, on the L-5-HTP-induced increases in cortisol and PRL secretion, was examined in 12 normal male volunteers. Pretreatment with pindolol, 30 mg orally, significantly inhibited the PRL but not the cortisol response to L-5-HTP, 200 mg PO. Pindolol alone decreased basal plasma PRL levels and increased basal plasma cortisol levels, possibly due to 5-HT1A antagonist and agonists effects, respectively. These data, coupled with observations from other studies, suggest that the L-5-HTP-induced increase in PRL but not cortisol secretion requires 5-HT1A receptor activation. PRL secretion due to 5-HT formed from exogenous L-5-HTP may require the availability of both intact 5-HT1A and 5-HT2/5-HT1C receptors, since blockade of either receptor type inhibited the PRL response to L-5-HTP. The implication of this synergistic effect for interpretation of neuroendocrine studies involving the serotonergic system in man is discussed.
Laboratory of Biological Psychiatry, Case Western Reserve University, Cleveland, OH 44106.
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Meltzer
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D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000328:Adult; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism
D011985:Receptors, Serotonin; D011388:Prolactin; D010869:Pindolol; D006916:5-Hydroxytryptophan; D006854:Hydrocortisone