Interaction of Growth Hormone-Releasing Factor (GRF) and 14 GRF Analogs with Vasoactive Intestinal Peptide (VIP) Receptors of Rat Pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(l-29)-NH2as a VIP Antagonist*
- 1 June 1985
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 116 (6), 2643-2649
- https://doi.org/10.1210/endo-116-6-2643
Abstract
Adenylate cyclase stimulation by GH [growth hormone] releasing factor (GRF) and 14 GRF analogs ([hp[human pancreatic]GRF(1-29)-NH2; (D-Tyr1)-GRF(1-29)-NH2; (D-Ala2)-GRF(1-29)-NH2; (D-Asp3)-GRF(1-29)-NH2; (D-Ala4)-GRF(1-29)-NH2; (D-Phe6)-GRF(1-29)-NH2; (D-Thr7)-GRF(1-29)-NH2; (N-Ac-Tyr1)-GRF(1-29)-NH2; (N-Ac-Tyr1,D-Ala2)-GRF(1-29)-NH2; (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2; (N-Ac-Tyr1-D-Phe2)-GRF(1-29)-NH2; (N-Ac-Tyr1-Trp6)-GRF(1-29)-NH2; (Phe1)-GRF(1-29)-NH2; (Phe4-GRF(1-29)-NH2; and (pCl-Phe6)-GRF(1-29)-NH2] modified in the N-terminal part) was compared to the capacity of the same peptides to inhibit [125I]iodo-vasoactive intestinal peptide (VIP) binding in rat pancreatic plasma membranes. These peptides interfered with VIP receptors as they inhibited [125I]iodo-VIP binding, and probably acted through VIP-preferring receptors as 1 of these peptides [(N-Ac-Tyr1D-Phe2)-GRF(1-29)-NH2] selectively inhibited both VIP- and GRF-stimulated adenylate cyclase activities. In general, alterations in positions 6 and 7 (but not in positions 1-4) markedly reduced the affinity of the resulting GRF analog [based on Kact (concentration exerting half-maximal stimulation) values]. The intrinsic activity exerted by GRF analogs on adenylate cyclase was reduced by acetylation of the free NH2 group and by the replacement of Asp3, Ala4, Phe6, and Thr7 by the corresponding D-isomer. The presence of pCl-Phe6 and Trp6 also depressed this parameter. Substitution in GRF (or its N-acetylated derivative) by D-Phe2, D-Arg2, and D-Ala4 again reduced the intrinsic activity, whereas substitution of the natural L-amino acid residue by D-Ala2 and Phe4 gave superagonists.This publication has 13 references indexed in Scilit:
- Growth Hormone-Releasing Factor from a Human Pancreatic Tumor That Caused AcromegalyScience, 1982
- Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumorBiochemistry, 1982
- BIDIRECTIONAL COLLISION COUPLING IN THE REGULATION OF THE ADENYLATE-CYCLASE - THE ALLOZYME HYPOTHESIS FOR RECEPTOR FUNCTION1982
- Structural requirements for glucagon receptor binding and activation of adenylate cyclase in liver. Study of chemically modified forms of the hormone, including N alpha-trinitrophenyl glucagon, an antagonist.Journal of Biological Chemistry, 1981
- Glucagon: Structure-Function Relationships Investigated by Sequence DeletionsHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1981
- Glucagon amino groups. Evaluation of modifications leading to antagonism and agonism.Journal of Biological Chemistry, 1980
- Secretin and VIP-stimulated adenylate cyclase from rat heartPflügers Archiv - European Journal of Physiology, 1980
- SOLID‐PHASE SYNTHESIS OF PORCINE VASOACTIVE INTESTINAL PEPTIDEInternational Journal of Peptide and Protein Research, 1980
- Subcellular Distribution and Response to Gastrointestinal Hormones of Adenylate Cyclase in the Rat Pancreas Partial Purification of a Stable Plasma Membrane PreparationEuropean Journal of Biochemistry, 1976
- RECEPTOR RESERVE AND THRESHOLD PHENOMENA .1. THEORY AND EXPERIMENTS WITH AUTONOMIC DRUGS TESTED ON ISOLATED ORGANS1960