BINDING-SITES FOR GROWTH HORMONE-RELEASING PEPTIDE

Growth hormone-releasing peptides (GHRPs) are known to release growth hormone (GH) in vivo and in vitro by a direct action on receptors in a nterior pituitary cells. Measurement of second messengers released fol lowing somatotroph stimulation suggests the existence of more than one GHRP receptor subtype in the hypothalamic-pituitary system. Furthermo re, hexarelin, a hexapeptide of the GHRP family and a potent GH secret agogue, is reported to increase left ventricular ejection fraction, su ggesting the expression of specific myocardial GHRP binding sites. In order to confirm such a hypothesis, a photoactivatable derivative of h exarelin, Tyr-p-benzoyl phenylalanine-Ala-hexarelin, was developed. A putative GHRP receptor with an apparent relative molecular mass of 57 000 was specifically labelled and characterized in human, bovine and p orcine anterior pituitary membranes using this hexarelin derivative. T he existence of myocardial binding sites was also demonstrated using t he same approach. The differential binding affinity of GHRP analogues to cardiac tissue raises the possibility of the existence of distinct GHRP receptor subtypes in the pituitary and the cardiovascular system, for which physiological roles have yet to be determined.