Home
Resources
Publications
Mechanism of Action of des-His1-[Glu9]glucagon Amide, a Peptide Antagonist of the Glucagon Receptor System

Mechanism of Action of des-His1-[Glu9]glucagon Amide, a Peptide Antagonist of the Glucagon Receptor System

S R Post, P G Rubinstein, H S Tager

Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1662-6.

PMID: 8383321

Abstract:

We have investigated the mechanisms through which des-His1-[Glu9]glucagon amide functions as a peptide antagonist of the glucagon receptor/adenylyl cyclase system. Studies with radiolabeled peptides identified that (i) the antagonist bound to intact hepatocytes according to a single first-order process, whereas the rate of association of glucagon with the same preparation could be described only by the sum of two first-order processes; (ii) the interaction of the antagonist with saponin-permeabilized hepatocytes was not affected by the addition of GTP to the incubation medium or by the elimination of Mg2+, whereas the interaction of glucagon with the same cell preparation was modified significantly by the presence of the nucleotide or by the absence of the divalent metal ion; (iii) the dissociation of antagonist from intact hepatocytes incubated in buffer was complete, whereas that of agonist was not; and (iv) the antagonist bound to intact hepatocytes at steady state according to a single binding isotherm (as did both agonist and antagonist in permeabilized hepatocytes), whereas glucagon bound to the intact cell system with two clearly defined apparent dissociation constants. A model is presented for the mechanism of action of the glucagon antagonist in which the analog binds to glucagon receptors in a Mg(2+)- and GTP-independent fashion and in which resulting ligand-receptor complexes fail to undergo sequential adjustments necessary for the stimulation of adenylyl cyclase.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP110084952	[des-His1, Glu9]-Glucagon amide		110084-95-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: