TY - JOUR
T1 - An evaluation of intravenous, subcutaneous, and in vitro activity of new agmatine analogs of growth hormone-releasing hormone hGH-RH(1-29)NH2
AU - Kovacs, Magdolna
AU - Gulyas, Jozsef
AU - Bajusz, Sandor
AU - Schally, Andrew V.
N1 - Funding Information:
We thank Lea Percy for experimental assistance and the National Hormone and Pituitary Program (NHPP) for the gifts of materials used in radioimmunoassays. The work described in this paper was supported by a Grant from W.R. Grace & Co., the National Institutes of Health Grant DK 07467 (to A.V.S) and by the Medical Research Service of the Veterans Administration.
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(88)90621-2
DO - 10.1016/0024-3205(88)90621-2
M3 - Article
C2 - 2892105
AN - SCOPUS:0023850918
VL - 42
SP - 27
EP - 35
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 1
ER -