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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the functional properties of hepatic glucagon receptors during rat development. Glucagon binding to liver membranes and isolated hepatocytes was significantly less in foetuses and weaning rats than in adult animals, reflecting changes in the number of receptors rather than any change in receptor affinity for the hormone. After correcting for the smaller surface area of foetal hepatocytes, glucagon receptor concentrations were still lower in foetuses than in adult rats. The time courses of glucagon association to liver membranes and of glucagon receptor degradation of prenatal and postnatal rats were similar, while inactivation of glucagon by liver membranes was significantly lower in foetal than in adult rats. Also, glucagon-stimulated production of cAMP was smaller in younger rats. These findings suggest that, according to several criteria, glucagon receptors in the foetus are functionally normal and their delayed development may be important for the metabolic processes occurring during the perinatal age.
Mol Cell Endocrinol 1987 Feb
PMID:Characterization of glucagon receptors in liver membranes and isolated hepatocytes during rat ontogenic development. 303 Aug 50

Receptor binding assays demonstrate that bovine parathyroid hormone (PTH) and human PTH(1-34) can displace [125I]iodoglucagon from binding to its receptor in rat liver plasma membranes. The displacement of [125I]iodoglucagon requires several thousand-fold more bovine PTH or human PTH(1-34) than glucagon. However, the PTH peptides are more effective than secretin, which up to a concentration of 10(-5) M exhibits no ability to displace [125I]iodoglucagon. The greater potency of PTH compared with secretin occurs despite the fact that secretin shows a great deal of sequence homology with glucagon while PTH shows none. We demonstrate by circular dichroism that in the presence of 3 mM SDS glucagon and hPTH(1-34) have similar secondary structure contents, while secretin is more helical. Our results suggest that receptors can recognize gross conformational features of a peptide hormone in addition to interacting with a specific amino acid sequence. The ability of PTH to interact with glucagon receptors can be modulated by incorporation of charged amphiphiles into the plasma membrane. Negatively charged taurodeoxycholic acid increases the binding of the more cationic PTH while positively charged myristyltrimethylammonium bromide decreases this interaction. These effects demonstrate that receptor specificity can be modulated by its lipid environment and that electrostatic interactions between the hormone and the membrane surface can contribute to receptor binding.
Mol Cell Endocrinol 1987 Feb
PMID:Conformational determinants in receptor recognition of peptide hormones: interaction of parathyroid hormone with the glucagon receptor. 303 Aug 52

The roles of diacylglycerol (DAG), cAMP and Ca2+ in mediating the stimulatory action of arginine on pancreatic A cells have been investigated using phorbol esters, forskolin, a Ca2+ ionophore and trifluoroperazine (TFP). 0.5 microM 4 beta-phorbol 12-myristate 13-acetate (PMA) which stimulated glucagon secretion by approximately 3-fold in the absence of arginine, was unable to enhance arginine-stimulated glucagon secretion. Higher concentrations (1 and 10 microM) of PMA were able to enhance glucagon secretion in the presence of 1.25, 2.5, 5 but not 10 mM arginine. Insulin secretion was enhanced by PMA under all the conditions tested. Arginine (10 and 20 mM)-stimulated secretion of glucagon and insulin were synergistically augmented by 20 microM forskolin. While the effects of forskolin plus PMA on the A cells were additive, the effects of the two agents on the B cells were synergistic. The responses of the A and B cells to arginine required extracellular Ca2+. Secretion of the two hormones was dose-dependently stimulated by A23187. Arginine-stimulated glucagon secretion but not insulin secretion, was dose-dependently inhibited by TFP. These results suggest that proposed cellular second messengers interact differently in the A and B cells, and DAG and Ca2+ may play pivotal roles in mediating the actions of arginine on the A but not B cells; cAMP may play a modulatory role in the A cell response to arginine.
Mol Cell Endocrinol 1987 Mar
PMID:Role of second messengers in the regulation of glucagon secretion from isolated rat islets of Langerhans. 303 99

The effects of propylthiouracil (PTU) treatment on vasopressin, angiotensin II, glucagon and alpha 1-adrenergic receptors in both developing and adult rats were studied in liver membrane preparations by measuring the binding of the following ligands: [3H][8-lysine]vasopressin, [3H]Sar-angiotensin II, [125I]glucagon and [3H]prazosin, and in the case of glucagon, by measuring adenylate cyclase activation. Whatever the ligand used, in young as well as in adult animals, PTU treatment led to a similar reduction (about 50%) in the maximal number of binding sites (Bmax), without significant changes in the apparent dissociation constant (KD) of labeled hormone for its specific receptor. In normal adult animals, thyroxine treatment, i.e. hyperthyroidism, had an opposite effect on the Bmax (25-50% increase), without changes in the KD. In developing PTU-treated rats, the abnormalities completely disappeared after therapy with increasing physiological doses of thyroxine; consequently they were directly related to thyroid deficiency and not to toxic effects of PTU. Moreover, the abnormalities resulting from induced hypothyroidism were reversible. In developing and adult hypothyroid rats, neither basal, NaF-, nor Gpp(NH)p-stimulated adenylate cyclase activities were significantly affected. Glucagon-sensitive adenylate cyclase activity seemed to be slightly increased (by about 15%), without changes in the apparent activation constant (Kact). These results are considered in parallel with findings on plasmatic glucagon and vasopressin levels, compared with similar previous reports related to renal vasopressin receptors, and discussed with respect to unpublished observations concerning hepatic responsiveness to glycogenolytic hormones in young and adult rats with induced hypothyroidism.
Mol Cell Endocrinol 1987 May
PMID:Comparative study of the developmental patterns of vasopressin, glucagon, angiotensin II, and alpha 1-adrenergic receptors in the liver of developing and adult hypothyroid rats. 303 20

The glucagon gene is expressed specifically in the alpha cells of the pancreatic islets. We show here that 300 base pairs of the 5'-flanking region of the rat glucagon gene, linked to a chloramphenicol acetyltransferase reporter plasmid transfected into islet cell lines of different hormone-producing phenotypes, directs transcription only in glucagon-producing islet cells. Deletional and linker-scanning mutations and DNase I footprinting assays identify three transcriptional control elements within these 300 base pairs. Two of these elements (G2 and G3) independently display enhancerlike functions on both homologous and heterologous promoters in glucagon (alpha) cells, but only on heterologous promoters in insulin- (beta) and somatostatin- (delta) expressing cells, and not in non-islet cells. The proximal promoter element (G1), characterized by low intrinsic transcriptional activity, is critical for specific expression of the glucagon gene in alpha cells. However, nuclear extracts prepared from all three islet cell phenotypes give similar protection to the three control elements of the glucagon 5'-flanking sequence. We conclude that these phenotypically distinct islet cell lines all contain regulatory DNA-binding proteins interacting with the three control elements of the glucagon gene, but that factors interacting with the glucagon promoter result in transcriptional activation only in alpha cells, to restrict glucagon gene expression to these cells. These observations suggest that interactions of nuclear proteins with cis-control elements are involved in the programmed developmental expression of the islet polypeptide hormone genes.
Mol Cell Biol 1988 Nov
PMID:Alpha-cell-specific expression of the glucagon gene is conferred to the glucagon promoter element by the interactions of DNA-binding proteins. 306 72

Glucagon decreases the activity of steroid-metabolising enzymes in isolated rat liver cells at physiological concentrations. Higher concentrations are less effective. TH-glucagon (1-N-alpha-trinitrophenylhistidine-12-homoarginine-glucagon) also reduces enzyme activity but does not lose activity at higher concentrations. The effects of the two hormones mimic closely their reported effects on phosphatidylinositol-4,5-bisphosphate breakdown. It is, thus, likely that the effect of glucagon on steroid metabolism is mediated via breakdown of this phospholipid. The calcium ionophore, A23187, had no effect on steroid metabolism whereas the phorbol ester 4 beta-phorbol-12-myristate-13-acetate (PMA) mimicked the effect of glucagon, showing that activation of protein kinase C but not Ca2+ mobilization may be involved in glucagon's action on hepatic steroid metabolism.
Mol Cell Endocrinol 1988 Feb
PMID:The effects of glucagon and TH-glucagon on steroid metabolism in isolated rat hepatocytes. 312 58

Inotropic responses to isoproterenol of hypertrophied hearts have been shown to be decreased. We have previously reported that in 13-week-old spontaneously hypertensive rats (SHR) this decrease is probably due to decreased beta-adrenergic receptor number, while in hearts from two kidney-one clip renal hypertensive rats (2K-1C RHR), this is due to a decreased nucleotide regulatory protein activity. We now show that changes in 2K-1C RHR are time dependent. One week after instituting development of hypertension the heart is already hypertrophied. Biochemical changes consistent with decreased glucagon receptors are seen, as well as beginning changes consistent with decreases in the nucleotide regulatory protein activity. By two weeks this is more evident. Hypertrophy and biochemical changes can be reversed up to six weeks, but by ten weeks the activity of the catalytic subunit of the adenylate cyclase system is decreased. In 1K-1C RHR, biochemical changes in the cyclase system are accelerated as compared with the 2K-1C model. In SHR, changes in 24-week-old rats are the same as in the 13-week-old rats. It is concluded that in cardiac hypertrophy associated with different models of hypertension the decreased inotropic responsiveness to isoproterenol is associated with different biochemical defects in the beta-adrenergic receptor response coupling pathway, and that reversal in function occurs only when there is no apparent change in the catalytic subunit of the adenylate cyclase complex.
J Mol Cell Cardiol 1985 Jun
PMID:Adenylate cyclase activity during development and reversal of cardiac hypertrophy. 316 Aug 64

The modulation of adenylate cyclase by guanosine triphosphate (GTP) and hormones was examined in liver membranes of lean and ob/ob mice, to determine whether a defective regulation of cyclase similar to that found in adipocyte membranes was present. In conjunction with GTP, glucagon was a powerful stimulant of cyclase in both types of membranes. In contrast, GTP alone or in conjunction with isoproterenol and norepinephrine stimulated significantly less in the membranes of the lean than in those of the obese mouse. In addition, low concentrations of norepinephrine elicited an inhibitory response in membranes of the lean mouse, but not in those of the obese. This inhibitory effect of norepinephrine was abolished by the alpha 2-antagonist yohimbine and by treatment with pertussis toxin, but not by propranolol or treatment with cholera toxin. These data show that it is possible to demonstrate inhibitory effects of guanine nucleotides on cyclase in the membranes from lean but not those from obese mice and suggest a defect in inhibitory regulation in the tissue of the obese.
Mol Cell Endocrinol 1988 Oct
PMID:The regulation of adenylate cyclase in liver membranes of lean and obese mice. 318 21

The fluorescence detected circular dichroism (FDCD) spectra of dansyl-leucine are reported. These spectra were obtained with the use of an unique device. FDCD, circular dichroism (CD) and absorption spectra of dansyl-leucine are combined to calculate CD spectra of the dansyl group in the given environment. A new method for determination of the secondary protein structure from the CD spectra taking into account the contribution of tryptophan residues is proposed. This contribution is defined from FDCD. The secondary structure of glucagon and human serum albumin, all containing a single, fluorescent tryptophan, were analysed. A good correspondence between these results and those reported for glucagon structure were found, while the usual method (without determination on tryptophan contribution) leads to unsatisfactory results.
Mol Biol (Mosk)
PMID:[Applicability of the fluorescence-detected circular dichroism method for the determination of the secondary structure of glucagon and albumin]. 337 88

The inotropic responses of chronic alcoholic and control rat hearts to phenylephrine, glucagon, ouabain, and dobutamine were studied to determine if the reported beta-adrenergic subsensitivity of alcoholic rat hearts was a specific defect. Male Long-Evans rats were maintained on nutritionally-complete liquid diets for 10 to 12 months; alcoholic rats received 38% of their calories from ethanol. Dry heart weight/body weight ratios indicated an average 15% hypertrophy of the alcoholic rat hearts. The function of isolated working hearts from these animals was studied at a constant heart rate and afterload. Ventricular function curves indicated significantly lower basal function of alcoholic rat hearts, as evident from their lower peak left ventricular relaxation rate, lower isovolumic relaxation rate, and lower peak power compared to controls. The alcoholic rat hearts had significantly lower inotropic (stroke work and peak power) responses to phenylephrine, glucagon, and dobutamine compared to controls, whereas the response of the alcoholics to ouabain was not significantly different from that of controls. Oxygen supply-to-utilization ratios decreased similarly in alcoholics and controls during treatment with the inotropic agents, as a result of increases in myocardial oxygen consumption and effects on coronary flow that were similar in both groups of animals. Thus the differences in inotropic responses observed with the alcoholic rat hearts were not primarily the result of compromised oxygen supply. Rather, the decreased stroke work response of the alcoholic hearts which occurred despite an increase in oxygen consumption suggested that the alcoholic rat hearts did not utilize oxygen as efficiently as did control hearts to perform external work. This was reflected in the significant differences between alcoholics and controls in the response of calculated external work efficiency to phenylephrine, glucagon, and dobutamine. Thus, alcohol-induced cardiac hypertrophy was associated with depressed basal left ventricular contractile function and decreased responsiveness to alpha 1-adrenergic, beta 1-adrenergic, and glucagon stimulation, but the responsiveness to ouabain was not significantly affected. These characteristics are similar to those of hearts hypertrophied by other causes.
J Mol Cell Cardiol 1987 Nov
PMID:Alcoholic cardiomyopathy in rats: inotropic responses to phenylephrine, glucagon, ouabain, and dobutamine. 343 59


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