Somatostatin octapeptides (lanreotide, octreotide, vapreotide, and their analogs) share the growth hormone-releasing peptide receptor in the human pituitary gland.
The binding affinity of somatostatin-14 (SRIF), various SRIF derivatives, and some peptides belonging to the growth hormone-releasing peptide (GHRP) family to specific receptors for SRIF and GHRP in the human pituitary gland has been measured. GHRP receptors have been identified using [125I]Tyr-Ala-hexarelin, a peptide that thas been demonstrated to be a potent growth hormone (GH) releaser in humans. Tyr-Ala-hexarelin binding was displaced in a dose-dependent manner by different GHRPs (hexarelin, GHRP-2, and EP-51216). Surprisingly, some SRIF octapeptide derivatives such as vapreotide, lanreotide, octreotide, and their analogs were also able to displace the GHRP ligand. By contrast, no inhibition of Tyr-Ala-hexarelin binding was observed in the presence of SRIF or SRIF derivatives (SRIF H-2186, H-2485, and H-3382) that are known to have a weak SRIF-like activity. When [125I]Tyr1-SRIF-14 was used as a ligand, we observed displacement with SRIF and the octapeptide SRIF analogs but not with GHRPs and other SRIF derivatives. The results point to a sharing of the GHRP receptor with the octapeptide SRIF analogs, but not SRIF. Our data are consistent with the hypothesis that the putative natural GH secretagogue ligand may be a growth hormone release inhibiting factor that is different from SRIF and that is antagonized by GHRP.
Deghenghi
R
R
Europeptides, Argenteuil, France. deghenghi@europeptides.com
Papotti
M
M
Ghigo
E
E
Muccioli
G
G
Locatelli
V
V
D000368:Aged; D000595:Amino Acid Sequence; D001344:Autopsy; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015282:Octreotide / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism*
D009842:Oligopeptides; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C086184:hexarelin; C060347:lanreotide; C051458:vapreotide; D013004:Somatostatin; D015282:Octreotide