Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland

Antagonism between GH secretagogues (GHS) and somatostatin (SRIH) has been postulated and demonstrated, but SRIH does not bind to GHS receptors (GHS-R ) and potent synthetic peptidyl GHS (GHRP6, hexarelin) do not displace radi olabeled SRIH from its receptors, However, non-natural SRIH octapeptide ago nists (mainly lanreotide and vapreotide) displace I-125-Tyr-Ala-hexarelin f rom pituitary binding sites suggesting that an endogenous factor related to SRIH might exist and interact with GHS-R, Our aims were to investigate the ability of different SRIH-like peptides such as various SRIH fragments (SR IH 3-14, SRIH 7-14, SRIH 3-10, SRIH 7-10, SRIH 2-9) and a natural neuropept ide that shows a high structural homology with SRIH such as cortistatin-14 (CST) to compete with I-125-Tyr-Ala-hexarelin for human pituitary binding s ites and to compare their binding affinity with that of hexarelin and ghrel in, a gastric-derived peptidyl GHS that has been proposed as a natural liga nd of GHS-R, While the binding of I-125-Tyr-Ala-hexarelin to pituitary memb ranes was completely displaced by unlabelled hexarelin, ghrelin and CST, no ne of the SRIH fragments tested inhibited this binding, Ghrelin and CST exh ibited a similar affinity (4.6-5.4 x 10(-7) mol/l) for the binding while he xarelin was more effective by about four orders of magnitude in displacing I-125-Tyr-Ala-hexarelin. Our data demonstrate for the first time that corti statin, a natural peptide related to SRIH, binds to GHS-R and suggest that this factor may play a role in modulating the activity of these receptors. (C) 2001, Editrice Kurtis.