EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Regulation of glucagon receptor binding lack of effect of magnesium and preferential role for gdp






Journal of Biological Chemistry 260(13): 7829-7835

Regulation of glucagon receptor binding lack of effect of magnesium and preferential role for gdp

The effects of Mg2+ and guanine nucleotides on glucagon binding to its receptor were studied using [125I-Tyr10] monoiodoglucagon. Contrary to findings with .beta.-adrenergic receptors, high affinity binding of the stimulatory hormone was not dependent on Mg2+ and low affinity binding could be obtained on nucleotide addition regardless of presence of Mg2+. GDP, guanyl-5'-yl thiophosphate (GDP.beta.S), GTP, and guanyl-5'-yl imidodiphosphate (GMP-P (NH)p) were all able to induce low affinity hormone binding. Since the Ns component of adenylyl cyclase, with which the receptor interacts, is inactive in stimulating the catalytic component C of adenylyl cyclase in the absence of Mg2+, both before and after GDP addition, it is suggested that Ns has at least 2 domains that change conformation independently of each other: a r domain, that interacts with the receptor and confers to it high affinity binding, and a c domain, that interacts with the catalyst C and stimulates it. Ns is r+ c- when stabilizing the receptor in its conformation with high affinity for hormone, and r-c- when under the influence of GDP which results in the receptor adopting the conformation that exhibits low affinity for the hormone. Comparison of potencies of the 4 nucleotides to induce low affinity binding showed that GDP and GDP.beta.S were equipotent and 10 times more potent than GTP and 100 times more potent than GMP-P(NH)P. Under the conditions used it was impossible to substantiate that the effects of GTP or GMP-P(NH)P were not due to formation of GDP from GTP or presence of GDP-like material in GMP-P(NH)P. Contrary to widely held opinions, GDP and GDP-like compounds, and not GTP or its analogs, are responsible for the lowering of the affinity of adenylyl cyclase stimulating receptors for their hormones or agonists. The c+ conformation of the c domain of Ns co-exists with the r+ and not the r- conformation of its r domain.


Accession: 006288033



Related references

Rojas, F.J.; Birnbaumer, L., 1985: Regulation of glucagon receptor binding. Lack of effect of Mg and preferential role for GDP. The effects of Mg2+ and guanine nucleotides on glucagon binding to its receptor were studied using [125I-Tyr10]monoiodoglucagon. Contrary to findings with beta-adrenergic receptors, high affinity binding of the stimulatory hormone was not dependen...

Sasaki, N.; Oshima, T.; Matsuura, H.; Yoshimura, M.; Yashiki, M.; Higashi, Y.; Ishioka, N.; Nakana, Y.; Kojima, R.; Kambe, M.; Kajiyama, G., 1997: Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes. The regulation of the intracellular concentration of Mg-2+ ((Mg-2+)-i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured (Mg-2+)-i and total Mg in rat lymphocytes by using, respectivel...

Swartz T.L.; Birnbaumer L., 1981: Iodine 125 labeled glucagon synthesis isolation by high pressure liquid chromatography and regulation of its binding by guanine nucleotides and magnesium ion. Federation Proceedings 40(6): 1878

Soman V.; Felig P., 1978: Down regulation of the glucagon receptor by physiologic hyper glucagonemia evidence of receptor and post receptor modulation of glucagon action. Clinical Research 26(3): 428A

Buggy, J.J.; Livingston, J.N.; Rabin, D.U.; Yoo Warren, H., 1995: Glucagon cntdot glucagon-like peptide I receptor chimeras reveal domains that determine specificity of glucagon binding. The binding of glucagon to its hepatic receptor triggers a G-protein-mediated signal that ultimately leads to an increase in hepatic glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis). In order to elucidate the structural...

Buggy, J.J.; Livingston, J.N.; Rabin, D.U.; Yoo-Warren, H., 1995: Glucagon.glucagon-like peptide I receptor chimeras reveal domains that determine specificity of glucagon binding. The binding of glucagon to its hepatic receptor triggers a G-protein-mediated signal that ultimately leads to an increase in hepatic glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis). In order to elucidate the structural...

Buggy, J.J.; Livingston, J.N.; Rabin, D.U., 1995: Glucagon glucagon-like peptide I receptor chimeras reveal domains that determine specificity of glucagon binding. The Journal of Biological Chemistry 270: 74-8

Wright, D.E.; Rodbell, M., 1980: Preparation of 2-thioltryptophan-glucagon and (tryptophan-S-glucagon)2. Differences in binding to the glucagon receptor in the hepatic adenylate cyclase system. The synthesis of 2-thioltryptophan-glucagon is described. Oxidation of this compound gives the dimer (Trp-S-glucagon)2. Both monomer and dimer are equi-potent on a molar basis with native glucagon as activators of adenylate cyclase in hepatic plas...

Gerich, J.E.; Lovinger, R.; Grodsky, G.M., 1975: Inhibition by somatostatin of glucagon and insulin release from the perfused rat pancreas in response to arginine, isoproterenol and theophylline: evidence for a preferential effect on glucagon secretion. To determine whether somatostatin inhibits glucagon secretion directly at the pancreatic level and to study quantitatively the relative effects of somatostatin on glucagon and insulin secretion, the effects of various concentrations of somatostati...

Unson, C.G.; Cypess, A.M.; Kim, H.N.; Goldsmith, P.K.; Carruthers, C.J.; Merrifield, R.B.; Sakmar, T.P., 1995: Characterization of deletion and truncation mutants of the rat glucagon receptor. Seven transmembrane segments are necessary for receptor transport to the plasma membrane and glucagon binding. Glucagon receptor mutants were characterized with the aim of elucidating minimal structural requirements for proper biosynthesis, ligand binding, and adenylyl cyclase coupling. One N-terminal deletion mutant and five truncation mutants with progre...