Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taken in physiological concentrations, glucagon increases the activity of adenylate cyclase from the heart of 11-day chick embryos, i.e. at the earliest investigated stage. High glucagon concentrations inhibit the enzyme from cardiac membranes at all ontogenetic stages except mature chicks in which glucagon produces stimulating effect. Guanine nucleotides potentiate this effect up to the 16th day of incubation, this effect being absent at later periods. Reconstruction of adenylate cyclase system from the heart of 16-day embryos with N-proteins from mature liver tissue of chicks results in the recovery of potentiating effect. However, at later developmental stages, potentiation was absent even in the presence of N-proteins.
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PMID:[The dual regulation by glucagon of the adenylate cyclase system in the embryonic chick heart]. 144 94

Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], probably representing an important incretin, binds to receptors on RINm5F cells resulting in an adenosine 3',5'-cyclic monophosphate increase. Guanine nucleotides (GTP, GTP-gamma-S, GDP-beta-S) decreased the binding of GLP-1(7-36)amide to receptors on RINm5F cell membranes. Further analysis revealed that GTP (10(-4) M) decreased the receptor affinity with an increase of the Kd from 2.5 +/- 0.99 x 10(-10) M to 9.43 +/- 2.16 x 10(-10) M. In cross-linking experiments the amount of labeled peptide linked to receptors was reduced in the presence of GTP (10(-4) M). Further studies investigated the involvement of membrane depolarization or changes in the cytosolic free calcium level in the intracellular signaling of GLP-1(7-36)amide-induced insulin secretion. In contrast to fuel and nonfuel secretagogues, GLP-1(7-36)amide did not cause a depolarization of the membrane potential. This was unaffected by various glucose concentrations (0-20 mM) or by previous cell depolarization by D-glyceraldehyde. Similarly, the cytosolic calcium concentration remained unchanged after addition of GLP-1(7-36)amide (10(-12)-10(-8) M). The effect of guanine nucleotides on binding of GLP-1(7-36)amide indicates that the action of the peptide is mediated by the adenylate cyclase system. GLP-1(7-36)amide binding neither changed the membrane potential nor altered the intracellular calcium concentration, making an involvement of the inositol 1,4,5-trisphosphate pathway or an activation of protein kinase C in the postreceptor signaling after GLP-1(7-36)amide binding unlikely.
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PMID:Signal transmission after GLP-1(7-36)amide binding in RINm5F cells. 255 Nov 82

The biochemical aspects of hepatic beta-adrenergic receptors and adenylate cyclase activity in male adult rats were examined during chronic treatment of a beta-adrenergic antagonist, propranolol. The blockade of beta-adrenergic nervous systems for 7 to 10 days produced a considerable elevation of basal, glucagon, sodium fluoride, and 5'-guanylylimidodiphosphate, Gpp (NH)p-stimulated enzyme activity with a negligible response to a beta-adrenergic agonist, isoproterenol. There was no alteration in the density or the affinity of beta-adrenergic receptors for the agonist during the treatment. Guanine nucleotides have failed to induce a transformation of the higher affinity to the lower affinity state of beta-adrenergic receptors of the hepatic membrane derived either from control or the propranolol-treated animals. The activity of stimulatory guanine nucleotide regulatory proteins (Ns) in the enzyme, assessed by ADP-ribosylation was also not altered by the antagonist. These results suggest that the mechanism of the observed sensitization of adenylate cyclase induced by chronic beta-adrenergic blockade involves facilitation of Ns interaction with the catalytic subunit of the enzyme with no change in the beta-adrenergic receptor functions.
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PMID:Effects of chronic propranolol treatment on hepatic adenylate cyclase system in the rat. 289 59

Guanine nucleotide and Mg2+ ion regulation of [125I-Tyr10]monoiodoglucagon ([125I]MIG) binding to liver plasma membranes from chicken, rat, and rabbit was studied. It was found that [125I]MIG binding to chicken liver membranes was increased by the addition of Mg2+ ion, while binding to rat and rabbit liver membranes was unaffected. In the chicken liver membranes, the Mg2+ ion induced high affinity binding which was sensitive to guanine nucleotides, while the low affinity binding in the absence of Mg2+ ion was not. Maximal effects of Mg2+ ion were observed at 1 mM. Glucagon binding to rat liver membrane receptors was GTP sensitive regardless of whether Mg2+ ion was added. Glucagon binding to rabbit liver membranes was insensitive to both Mg2+ ions and GTP. This lack of GTP effect was not due to degradation of GTP; no effect of the nonhydrolyzable analog guanyl-5'-yl-imidodiphosphate was observable. Glucagon stimulation of rabbit liver adenylyl cyclase, however, was dependent on GTP, as was the case with all of the other liver adenylyl cyclases studied here. The Kact of GTP for the rabbit liver system was very similar to that for rat liver membranes. The glucagon receptor was covalently labeled with [125I]MIG using p-hydroxysuccinimidyl azidobenzoate and analyzed by sodium dodecyl sulfate-gel electrophoresis. In all cases, a major labeled band at 63,000 daltons was observed. The levels of glucagon receptor and stimulatory (Ns) and inhibitory (Ni) regulatory proteins of adenylyl cyclase were measured. The highest levels of glucagon receptor were measured in rat liver membranes, while the levels in chicken and rabbit membranes were 30-40% lower. Rabbit liver membrane had the highest levels of Ns, while rat liver membranes had 2-fold lower and chick liver membrane 4-fold lower levels than rabbit liver membranes. The levels of Ni was similar in the three systems. Thus, the ratio of Ns to glucagon receptor was highest in the rabbit. In the rat, this ratio was 3-fold lower than that in the rabbit. In the chicken membranes, the ratio was about 60% of that in the rat. These data suggest that the observed differences in effects of GTP on hormone binding can be explained by alterations in the ratio of the receptor and Ns proteins among the various species.
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PMID:The hepatic glucagon receptor: a comparative study of the regulatory and structural properties. 303 85

Membrane-bound adenylate cyclase (AC) activity was much higher in the presence of Mn2+ than of Mg2+. The Mn2+-sensitive adenylate cyclase (MnAC) showed a linear rate of activity for at least 60 min. In contrast, the Mg2+-sensitive AC (MgAC) displayed a considerable burst in activity, so that after 90 min of activity it was approximately tenfold higher than at the start of incubation. Guanine nucleotides enhanced MgAC activity; 10(-6) to 10(-5) M of 5'-guanylylimidodiphosphate caused a threefold stimulation. The MgAC could be stimulated by hormones (FSH, hCG, PGE1, isoproterenol, glucagon), the highest activation being achieved with FSH. Increasing levels of ATP produced a concentration-dependent increase in MgAC activity. The apparent affinity of the AC for MgATP increased threefold (Km 0.50-0.15 mM) by raising the free Mg2+ concentration from 0.4 to 10.0 mM. The membrane-bound AC of the blue fox testis is thus regulated by hormones, Mg2+, and guanine nucleotides in a similar manner to ACs in other somatic cells and in testes from other species. The high MnAC activity in membrane particles from these testes probably represents membrane-bound AC activity in germ cells. The burst in MgAC activity during incubation may represent proteolytic activation of membrane-bound germ cell AC, with a gradual appearance of Mg2+ sensitivity.
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PMID:Membrane-bound adenylate cyclase activity in the testis of the blue fox. 393 98

Guanine nucleotides were observed to modify the binding of 125I-angiotensin II to rat hepatic plasma membrane receptors. GTP and its nonhydrolyzable analogues greatly increased the dissociation rate of bound 125I-angiotensin II and altered hormone binding to the receptor under equilibrium conditions. In the absence of GTP, 125I-angiotensin II labeled both high affinity sites (Kd1 = 0.46 nM, N1 = 650 fmol/mg) and low affinity sites (Kd2 = 4.1 nM, N2 = 1740 fmol/mg). In the presence of guanine nucleotides, the affinities of the two sites were unchanged, but the number of high affinity sites decreased markedly to 52 fmol/mg. In analogous experiments using the angiotensin II antagonist, 125I-sarcosine1,Ala8-angiotensin II (125I-saralasin), guanine nucleotides minimally affected the interaction of 125I-saralasin with its receptor, increasing the dissociation rate 1.9-fold and the Kd 1.4-fold. The guanine nucleotide inhibition of agonist binding required a cation such as Na+ or Mg2+, with a maximal effect occurring at about 1 mM Mg2+. In liver plasma membranes prepared in EDTA, angiotensin II inhibited basal and glucagon-stimulated adenylate cyclase activities by 30% and 10%, respectively. Angiotensin II also caused a 40% inhibition of glucagon-stimulated cyclic AMP accumulation in intact hepatocytes, with a half-maximal effect occurring at 1 nM. The inhibition by angiotensin II of adenylate cyclase in membranes and of cAMP levels in intact cells could be reversed by the antagonist sarcosine1,Ile8-angiotensin II. Vasopressin caused a smaller 26% inhibition of glucagon-stimulated cyclic AMP accumulation. The ability of angiotensin II to inhibit cyclic AMP synthesis may provide an explanation for the observed effects of guanine nucleotides on 125I-angiotensin II binding to plasma membranes.
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PMID:The hepatic angiotensin II receptor. II. Effect of guanine nucleotides and interaction with cyclic AMP production. 627 54