A non-opioid pattern characterizes inhibition of growth hormone releasing peptide binding by dynorphin-related peptides.
GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-LysNH2; SK&F 110679) is a hexapeptide that specifically releases growth hormone. Although derived from methionine enkephalin, 3H-SK&F 110679 binding profiles suggest that it retains little mu or delta opioid activity. In the present study, dynorphin A was a potent inhibitor of SK&F 110679 binding. However, detailed structure-activity studies using dynorphin-related compounds suggest that the interaction between SK&F 110679 and dynorphin was non-opioid in nature. The non-opioid peptide des-Tyr-dynorphin was virtually as potent an inhibitor of 3H-SK&F 110679 binding as the intact dynorphin peptide. Additionally, the non-peptide, kappa selective ligand U-50,488 was a very weak inhibitor of 3H-SK&F 110679 binding. Since dynorphin but not U-50,488 has been reported to release growth hormone, the present results suggest that a non-opioid dynorphin site participates in SK&F 110679's growth hormone releasing action.
Codd
E E
EE
R. W. Johnson Pharmaceutical Research Institute, Department of Biological Science, Springhouse, PA 19477-0776.
Aloyo
V J
VJ
Walker
R F
RF
D000818:Animals; D001667:Binding, Competitive; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D006728:Hormones; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D004399:Dynorphins; D013007:Growth Hormone-Releasing Hormone