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 anterior pituitary cells. Measurement of second messengers released following somatotroph stimulation suggests the existence of more than one GHRP receptor subtype in the hypothalamic-pituitary system. Furthermore, hexarelin, a hexapeptide of the GHRP family and a potent GH secretagogue, is reported to increase left ventricular ejection fraction, suggesting the expression of specific myocardial GHRP binding sites. In order to confirm such a hypothesis, a photoactivatable derivative of hexarelin, 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 porcine anterior pituitary membranes using this hexarelin derivative. The existence of myocardial binding sites was also demonstrated using the 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.
Ong
H
H
Faculty of Pharmacy, University of Montreal, Québec, Canada.
Bodart
V
V
McNicoll
N
N
Lamontagne
D
D
Bouchard
J F
JF
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D019920:Photoaffinity Labels; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000145:classification / Q000378:metabolism*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000145:classification / Q000378:metabolism*; D013552:Swine
D007457:Iodine Radioisotopes; D009842:Oligopeptides; D019920:Photoaffinity Labels; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C086184:hexarelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor