The rapid desensitization of glucagon-stimulated adenylate cyclase is a cyclic AMP-independent process that can be mimicked by hormones which stimulate inositol phospholipid metabolism (original) (raw)
Related papers
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1984
Na-Trinitrophenylhistidine,12-homoarginine]glucagon (THG) is a potent antagonist of the effects of glucagon on liver membrane adenylate cyclase. In isolated hepatocytes, this glucagon analogue was an extremely weak partial agonist for cAMP accumulation, and it blocked the stimulation of cAMP accumulation produced by glucagon. However, THG was a full agonist for the stimulation of glycogenolysis, gluconeogenesis and urea synthesis in rat hepatocytes, and did not antagonize the metabolic effects of glucagon under most of the conditions examined. Forskolin potentiated the stimulation of cAMP accumulation produced by glucagon or THG, but did not potentiate their metabolic actions. A much larger increase in cAMP levels seemed to be required for the stimulation of hepatocyte metabolism by forskolin than by glucagon or THG. This may suggest the existence of a functional compartmentation of cAMP in rat hepatocytes. The possible existence of compartments in cAMP-mediated hormone actions and the involvement of factors, besides cAMP, in mediating the effects of THG and glncagon is suggested.
Glucagon and epinephrine stimulation of adenyl cyclase in isolated rat liver plasma membranes
Biochemical and Biophysical Research Communications, 1969
Adenyl cyclase has been shown to be specifically localized in the plasma membrane of rat liver. The activity of this enzyme is stimulated by glucagon and epinephrine in isolated plasma membrane systems. The stimulation by epinephrine has a lag period of about 10 minutes. Epinephrine shows selective binding to isolated plasma membranes. The results indicate that epinephrine binds to a receptor protein rather than interacting directly with the enzyme adenyl cyclase. Calcium ions also stimulate adenyl cyclase in isolated plasma membranes but the effect shows appreciable variability. The biological significance of cyclic AMP (adenosine-3',5'-monophosphate)
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1970
Membrane bound adenyl cyclase in isolated rat liver plasma membranes exhibits a requirement for Mg 2+ and has optimal activity near pH 8.0. The optimal concentration of ATP is approx. 0.3 mM at a Mg ~+ concentration of i.o raM. Ca 2+ at a concentration range of 0.03-0.3 mM stimulates the basal activity of this enzyme. The enzyme activity is abolished by I rain heating at IOO °. Detergents such as Triton X-ioo and sodium dodecyl sulfate alter the membrane structure and slightly enhance the enzyme actively, whereas sodium deoxycholate slightly inhibits the enzyme. Glucagon and epinephrine stimulate whereas insulin inhibits adenyl cyclase activity. When studied under identical conditions on the same membrane preparation the glucagon stimulation is seen earlier and at lower hormone concentration (I-lO-6 M) than is the epinephrine stimulation which requires lO .5 M hormone. The inhibition by insulin is seen at I. lO-5 M or greater. The stimulation by glucagon is inhibited by i-lO-4-1 • lO-5 M Ca 2+ but the stimulation by epinephrine is enhanced by I. IO-4-I-IO-~ M Ca ~+. Moreover, epinephrine enhances, whereas glucagon inhibits the binding of Ca 2+ to the membrane. Studies on the combined effects of the hormones show that the stimulation by glucagon plus epinephrine is not additive and that insulin antagonizes the glucagon stimulation of adenyl cyclase. Na + inhibits the basal activity of adenyl cyclase but K + stimulates the enzyme. F-inhibits the enzyme. These results point to a complex interplay of hormones and metal ions with the membrane bound adenyl cyclase. * The validity of the two-dimensional chromatographic assay for cyclic AMP is based on the following: (a) co-chromatography with authentic 3',5'-cyclic AMP, (b) the hydrolysis of cyclic AMP to 5'-AMP by brain phosphodiesterase and (c) the complete separation of cyclic AMP from ATP, ADP, 5'-AMP, adenosine, adenine, hypoxanthine, inosine, inosinic acid, ribose and ribose phosphate.
FEBS Letters, 1993
Two cyclic AMP analogues, l-chloro cyclic AMP and 8-(4 chlorophenyltbio) cyclic AMP, were found to increase the incorporation of rHJoleate into cholereryl ester in cultured hamster hapatocytes (30-40%), while incorporation into triacylglycerol was unaffected. An increase of a similar magnitude was observed in the presence of glucagon and the phosphodiesterase inhibitor, theophylline. The cyclic AMP analogues also stimulated the activity of neutral cholesteryl ester hydrolase in the cells, and this effect was mimicked by glucagon and theophylline. These results show that cyclic AMP can affect the cholesteryl ester cycle in hamster hepatocytes, and support the idea that the enzymes involved may be co-ordinately regulated.
Biochimica Et Biophysica Acta-biomembranes, 1976
1. Activation of adenylate cyclase in rat liver plasma membranes by fluoride or GMP-P(NH)P yielded linear Arrhenius plots. Activation by glucagon alone, or in combination with either fluoride or GMP-P(NH)P resulted in biphasic Arrhenius plots with a well-defined break at .2. The competitive glucagon antagonist, des-His-glucagon did not activate the adenylate cyclase but produced biphasic Arrhenius plots in combination with fluoride or GMP-P(NH)P. The break temperatures and activation energies were very similar to those observed with glucagon alone, or in combination with either fluoride or GMP-P(NH)P.3. It is concluded that although des-His-glucagon is a potent antagonist of glucagon, it nevertheless causes a structural coupling between the receptor and the catalytic unit.