title: An evaluation of intravenous, subcutaneous, and in vitro activity of new agmatine analogs of growth hormone-releasing hormone hGH-RH (1-29)NH2.
abstract: The effects of new Agmatine (Agm) analogs of human growth hormone-releasing hormone (GH-RH) were compared to GH-RH (1-29)NH2 and to (D-Ala2)GH-RH(1-29)NH2 after intravenous (IV) and subcutaneous (SC) administration to pentobarbital-anesthetised male rats and in vitro using superfused rat pituitary cell system. After IV administration, the analogs: (D-MeAla2,Nle27)GH-RH(1-28)Agm(JG-75), (desamino-Tyr1,D-Ala2,Nle27)GH-RH(1-28)Agm(JG-77), (D-Ala2,Nle27)GH-RH(1-28)Agm(JG-73) and (D-Ala2)GH-RH(1-29)NH2 showed a potency 2.6-3.9 times greater than GH-RH(1-29)NH2 at 5 min and 1.6-2.7 times higher at 15 min. After SC administration these analogs were 30-74 times more potent than GH-RH(1-29)NH2. The ratio between the IV and SC GH-releasing activity of the analogs ranged from 2 to 5, while GH-RH(1-29)NH2 was about 50 times more active IV than SC. This indicates that 20-50% of the analogs can be absorbed from SC tissues, but only 2% of GH-RH(1-29)NH2. The in vitro activity of the agmatine analogs on GH release closely paralleled their IV potency and was 2.8-3.9 times greater than that of GH-RH(1-29)NH2. No significant difference in potency was found between (D-Ala2)GH-RH(1-29)NH2 and JG-75 after IV administration and in vitro, although JG-75 contained only 28 amino acids. We conclude that the reason for the large discrepancies between the previously reported activities of (D-Ala2)GH-RH(1-29)NH2 was simply due to the different ways of administration of this analog, SC vs IV, and not to species specificity. The replacement of Arg29 by Agmatine in (D-Ala2,Nle27)GH-RH(1-29)NH2 causes a 3 fold increase in SC potency, but the replacement of D-Ala2 with D-MeAla2 reduces the SC, but not the IV and in vitro activity in half.
mesh_terms: D000376:Agmatine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001120:Arginine; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017337:Sermorelin
chemical_list: D006146:Guanidines; D010446:Peptide Fragments; D000376:Agmatine; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine