Influence of beta-adrenergic agonists and antagonists on the GH-releasing effect of Hexarelin in man.
Beta-adrenergic receptors mediate the inhibitory influence of cathecolamines on GH secretion, probably via the stimulation of hypothalamic somatostatin release. Accordingly, beta-adrenergic agonists and antagonists inhibit and increase, respectively, the GH response to many stimuli, including GHRH, in man. Aim of the present study was to verify the effect, if any, of beta-adrenergic drugs on the GH response to Hexarelin, a synthetic GH-releasing hexapeptide. Interestingly, the GH-releasing effect of Hexarelin has been reported to be partially refractory to neuroendocrine manipulations known to strongly enhance or abolish the GHRH-induced GH release. In 6 normal male volunteers (aged 22-27 yr) we studied the interaction of the maximally effective iv dose of Hexarelin (HEX, 2 micrograms/kg iv at 0 min) with atenolol (100 mg po at -60 min) or salbutamol (0.08 mg/kg po at -60 min), which are beta-adrenergic antagonist and agonist, respectively. HEX induced a marked GH rise (AUC, mean +/- SE: 4573.2 +/- 588.8 micrograms.min/L), which was unchanged by atenolol (4706.2 +/- 928.2 micrograms.min/L) but blunted by salbutamol (2792.8 +/- 618.0 micrograms.min/L, p < 0.03). In conclusion, present data show that, in man, the GH-releasing effect of Hexarelin is not enhanced by beta-adrenergic blockade while is only blunted by the activation of beta receptors. According to other data, these results indicate that the potent GH-releasing activity of Hexarelin is, at least partially, refractory to beta-adrenergic-mediated manipulations of somatostatinergic activity.
Arvat
E
E
Dipartimento di Fisiopatologia Clinica, University of Torino, Italy.
Gianotti
L
L
Ramunni
J
J
DiVito
L
L
Deghenghi
R
R
Camanni
F
F
Ghigo
E
E
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D000595:Amino Acid Sequence; D001262:Atenolol / Q000494:pharmacology; D004347:Drug Interactions; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D009842:Oligopeptides; C086184:hexarelin; D001262:Atenolol; D013006:Growth Hormone; D000420:Albuterol