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 hormone receptor coupling to adenylate cyclase effects of gtp and gdp


Journal of Biological Chemistry 255(21): 10312-10321
Regulation of hormone receptor coupling to adenylate cyclase effects of gtp and gdp
GDP and GTP regulation of receptor-mediated stimulation of adenylate cyclase [AC] in membranes of murine lymphoma cells (S49), NS-20 murine neuroblastoma cells (NS-20), rabbit corpora lutea (CL) and turkey erythrocytes were studied under assay conditions, which minimized conversion of added GTP to GDP and of added GDP to GTP. Hormonal stimulation in all systems required guanine nucleotide addition. In the presence of GTP, AC activity in S49, NS-20, and CL was stimulated, respectively, by isoproterenol and prostaglandin E1 (PGE1); by PGE1 and the adenosine analog, phenylisopropyladenosine; and by PGE1 and isoproterenol.sbd.the first of the listed stimulants eliciting higher activities than the second. Activity in turkey erythrocyte membranes was stimulated by isoproterenol. GDP was partially effective in promoting hormonal stimulation, being able to sustain stimulation by isoproterenol and PGE1 in S49 cell membranes, and by PGE1 in CL membranes. In NS-20 membranes, both GDP and guanosine-5'-O-(2-thiodiphosphate) (GDP.beta.S) were inhibitory on basal activity, yet promoted limited but significant stimulation by PGE1. In turkey erythrocytes, stimulation by isoproterenol could not be elicited with GDP or GDP.beta.S. Although less effective than GTP in promoting hormonal stimulation of several AC systems, GDP was clearly not inactive. Concentration effect curves for active hormone in the presence of GDP had higher apparent Ka values than in the presence of GTP. In spite of differences between the effects of GTP and GDP on hormonal stimulation of AC activities, GTP and GDP affected equally well isoproterenol binding, regardless of whether or not its receptor could be shown to stimulate AC in the presence of GDP. Determination of transphosphorylation of GDP to GTP showed that, at saturating concentrations, the proportion of GDP converted to GTP is negligible and unaffected by hormonal stimulation. Concentrations giving 50% inhibition were determined for GTP- and GDP-mediated inhibition of guanyl-5'-yl imidodiphosphate stimulation in the absence and presence of stimulatory hormones. In all 4 systems studied, GTP and GDP interacted with about equal potency and hormonal stimulation was not accompanied by a selective decrease in affinity for GDP. One way to explain the results obtained is to view hormonally sensitive AC systems as 2-state enzymes: the activities are regulated by GTP and GDP through an allosteric site related to the catalytic moiety, and receptors are entities that are inactive and, hence, unable to couple unless occupied by hormones and activated by any guanine nucleotide through a distinct receptor-related process.


Accession: 006288498



Related references

Coupling of the glucagon receptor to adenylate cyclase ec 4.6.1.1 by gdp evidence for 2 levels of regulation of adenylate cyclase. Proceedings of the National Academy of Sciences of the United States of America 76(7): 3189-3193, 1979

Agonist regulation of adenylate cyclase activity in neuroblastoma x glioma hybrid NG108-15 cells transfected to co-express adenylate cyclase type II and the beta 2-adrenoceptor. Evidence that adenylate cyclase is the limiting component for receptor-mediated stimulation of adenylate cyclase activity. Biochemical Journal 318: 1033-1039, 1996

Neuro hypophyseal hormone responsive renal adenylate cyclase part 4 a random hit matrix model for coupling in a hormone sensitive adenylate cyclase system. Journal of Biological Chemistry 253(9): 3238-3250, 1978

Kinetics of adenylate cyclase regulation in intact cultured heart cells evidence for close receptor cyclase coupling. American Heart Association Monograph (114): III-331, 1985

Regulation of hormone-receptor coupling to adenylyl cyclase. Effects of GTP and GDP. Journal of Biological Chemistry 255(21): 10312-10321, 1980

Pseudohypoparathyroidism: deficiency of hormone receptor-adenylate cyclase coupling protein as a cause of hereditary hormone resistance. Progress in Clinical and Biological Research 97: 327-340, 1982

Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism. American Journal of Physiology 243(1): E37-E42, 1982

Regulation of adenylate cyclase system of Tetrahymena pyriformis by hormone and non-hormone agents and its dependency on adenylate cyclase basal activity. Zhurnal Evoliutsionnoi Biokhimii i Fiziologii 39(4): 332-338, 2003

Mechanisms of hormone receptor-effector coupling: the beta-adrenergic receptor and adenylate cyclase. Federation Proceedings 41(10): 2664-2670, 1982

Molecular mechanisms of coupling in hormone receptor-adenylate cyclase systems. Advances in Enzymology and Related Areas of Molecular Biology 53: 1-43, 1982