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)

Heterogeneity in Madin-Darby canine kidney (MDCK) epithelial cells has been reported, however, its details have not been well described. In the present study, we show that subclones obtained from a MDCK cell line could be divided into two morphologically and biochemically distinct cell types with different hormonal responsiveness. Clones of the first type, motile clones, which had extended and flattened cytoplasm, were devoid of carbonic anhydrase activity. Clones of the second type, nonmotile clones, formed colonies of cuboidal cells and showed carbonic anhydrase activity. Motile clones synthesized cAMP in response to arginine vasopressin, prostaglandin E1, and isoproterenol but not glucagon. In contrast, nonmotile clones responded to all of these hormones. These findings suggest MDCK cells have multiple cellular origins. The motile clones have characteristics similar to the principal cells of the collecting system, whereas the nonmotile clones may be derived from the thick ascending limb or the intercalated cell. Our studies also demonstrate a significant influence of culture condition on MDCK cellular behavior (carbonic anhydrase activity, Na+/K+-ATPase activity and vasopressin responsiveness). Therefore, physiologic and biochemical experiments with MDCK cells must be interpreted with reservations about cellular heterogeneity as well as differences induced by culture conditions.
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PMID:Characterization of subclones of Madin-Darby canine kidney renal epithelial cell line. 255 8

1. A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea-pigs to assess the possible participation of cardiac, capsaicin-sensitive, substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5-hydroxytryptamine (5-HT), histamine, prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), prostaglandin F2 alpha, (PGF2 alpha), adrenaline (Ad), glucagon, nicotine and angiotensin II (AII). 2. The positive chronotropic and inotropic effects of Bk, Kd and 5-HT were markedly reduced in capsaicin-desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36-81% (chronotropic effect) and 62-86% (inotropic effect); for Kd: 61-78% (chronotropic effect) and 53-77% (inotropic effect); for 5-HT: 25-66% (chronotropic effect) and 40-64% (inotropic effect]. 3. The positive chronotropic and inotropic effects of histamine, PGE1, PGE2, PGF2 alpha, glucagon and AII had similar amplitudes in capsaicin-desensitized and control atria. 4. The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 x 10(-7) and 7.5 x 10(-6) M Ad were reduced by 41 and 27% respectively, in capsaicin-desensitized atria compared to control. The chronotropic effects of 1.54 x 10(-5) and 6.17 x 10(-5) M nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin-desensitized and control atria. 5. These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5-HT in guinea-pig atria, unlike those of histamine, PGE1, PGE2 PGF2 alpha, glucagon and AII, might be the result of stimulation of capsaicin-sensitive, SP- and CGRP- containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin-sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea-pig atria.
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PMID:Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea-pig isolated atria. 272 Feb 92

The regulatory properties of adenylate cyclase in small intestinal mucosa were investigated. Glucagon, epinephrine and isoproterenol failed to activate the cAMP synthesis; prostaglandin E1 caused a 2.8-fold, while cholera toxin-a 4.5-fold stimulation. The latter was not able to increase the rate of glucose synthesis from alanine in vitro, but increased markedly the in vivo incorporation of 14C-labeled alanine into the mucus glucosamine. Unlabeled glucosamine excretion was also enhanced 3-fold. This provides evidence for the involvement of glycolysis and gluconeogenesis enzyme systems in the mucosal glycoprotein synthesis. It was assumed that both metabolic pathways may play a common physiological role, namely, to convert carbohydrates and gluconeogenic precursors into the substrate for glucosamine synthesis which is thought to be a rate-limiting step in small intestinal mucus secretion.
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PMID:[Relation between glycoprotein synthesis and carbohydrate metabolism in the small intestine mucosa. Effect of cholera enterotoxin]. 283 Sep 17

Several prostaglandins inhibit the cAMP response to glucagon and beta-adrenergic stimulation in hepatocytes. To probe the mechanism of this inhibition, we have examined in primary hepatocyte cultures how pretreatment with pertussis toxin (islet-activating protein) influences the ability of the cells to respond to hormones and prostaglandins. Pertussis toxin augmented the effects of glucagon, epinephrine and isoproterenol, and also markedly enhanced the cAMP response to prostaglandin E1 (PGE1). Furthermore, whereas PGE1, PGE2, PGI2 and PGF2 alpha attenuated the cAMP responses to glucagon in control cultures, this inhibition was abolished in cells pretreated with pertussis toxin. A more detailed comparison was made of the effects of PGE1 and PGF2 alpha. In cells not treated with pertussis toxin, both these prostaglandins at high concentrations reduced the cAMP response to glucagon and isoproterenol by approximately 50%, but dose-effect curves showed that PGE1 was about 100-fold more potent as an inhibitor than PGF2 alpha. Pertussis toxin abolished the inhibitory effects of PGE1 and PGF2 alpha with almost identical time and dose requirements. The results obtained with PGE1, PGE2, PGI2 and PGF2 alpha suggest that prostaglandins of different series attenuate hormone-activable adenylate cyclase in hepatocytes through a common mechanism, dependent on the inhibitory GTP-binding protein.
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PMID:Pertussis toxin abolishes the inhibitory effects of prostaglandins E1, E2, I2 and F2 alpha on hormone-induced cAMP accumulation in cultured hepatocytes. 283 60

We examined the effects of several neuroendocrine agents on the intracellular cyclic AMP level in cultured monkey trabecular meshwork cells. Among the peptide agonists studied, only the vasoactive intestinal peptide elevated the cyclic AMP level. Alpha-melanocyte stimulating hormone, glucagon, and others showed no stimulation. Prostaglandin E1 and L-isoproterenol also enhanced the intracellular cyclic AMP level. Such effects may implicate physiologic roles of these agonists in the trabecular meshwork.
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PMID:Effects of agonists on the intracellular cyclic AMP concentration in monkey trabecular meshwork cells. 283 41

We studied the molecular mechanisms of the abnormal response of the beta-adrenergic receptor-adenylate cyclase system in the myocardium of spontaneously hypertensive rats (SHR) by ADP-ribosylation catalyzed by cholera toxin and pertussis toxin, by reconstitutive assay of cardiac membranes with the human platelet membranes, and by immunostaining with polyclonal antibody against beta gamma-subunits of guanine nucleotide-binding proteins. The maximal activity of the enzyme stimulated by forskolin was higher in SHR than in control Wistar Kyoto (WKY) rats. However, the activity stimulated by isoproterenol, glucagon, histamine was similar for SHR and control rats. Moreover, the activity stimulated by PGE1 was lower in SHR than in control rats. The activity of the stimulatory guanine nucleotide-binding protein (Gs) of cholate extracted cardiac membranes from SHR was significantly lower than that from control rats. There were no strain differences in (1) number and affinity of beta-adrenergic receptors, (2) the function and amount of the inhibitory guanine nucleotide-binding protein (Gi), (3) substrates for cholera toxin catalyzed ADP-ribosylation, and (4) the amount of beta gamma-subunits of Gs and Gi. Thus, there is an abnormal signal transduction in beta-adrenergic receptor coupled adenylate cyclase system in SHR due to a reduction in the activity of the alpha-subunits of Gs.
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PMID:[Abnormalities in the beta-adrenergic receptor-adenylate cyclase system in the ventricular myocardium of spontaneously hypertensive rats]. 283 80

The effect of glucagon was studied on the isolated gastric fundus from immature rats in comparison with histamine. Glucagon (10(-7) -3 X 10(-6) M) caused a concentration-dependent increase in acid output, being approximately 25 fold more potent than histamine (ED50 values were 6.38 X 10(-7) M and 2.42 X 10(-5) M for glucagon and histamine, respectively). These compounds, however, did not differ in regard to the maximum response. The stimulatory effect of glucagon was not enhanced by pretreatment with 3 X 10(-8) M forskolin or 10(-7) M ICI 63197, a phosphodiesterase (PD) inhibitor. Conversely, both forskolin and ICI 63197 shifted to the left the concentration-response curve to histamine. The increase in acid secretion by glucagon was reduced by PGE1 (10(-5) M) and PGE2 (10(-5) M) but only PGE2 inhibited the response to histamine. From these data it can be concluded that glucagon stimulated acid production in the stomach from immature rats, and this effect does not seem to involve the same adenylate cyclase activated by histamine.
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PMID:Effect of glucagon on gastric acid secretion by the isolated fundus from immature rats. 283 65

Phosphorylation of the beta-adrenergic receptor (beta AR) is closely associated with homologous desensitization of the beta-adrenergic receptor-coupled adenylate cyclase system. Homologous desensitization and receptor phosphorylation also occur in cell mutants which are deficient in their cAMP-dependent protein kinase (kin- mutant of S49 lymphoma cells). beta AR phosphorylation is mediated by a cAMP-independent protein kinase which phosphorylates the receptor only when it is occupied by a beta-agonist. During the time course of desensitization the beta AR kinase (beta ARK) activity is translocated from a cytoplasmic to a plasma membrane location. beta ARK translocation can also be effected by prostaglandin E1 (PGE1) suggesting that this beta ARK may represent a more general enzyme capable of phosphorylating other adenylate cyclase-coupled receptors. Thus, beta ARK may play a key role in the process of homologous desensitization of adenylate cyclase coupled receptors. Extracellular hormones interact with specific receptors at the outer surface of the plasma membrane and thus initiate a cellular response. One of the best studied transmembrane signalling systems known to be coupled to the occupancy of cell surface receptors is adenylate cyclase. The adenylate cyclase system is composed of various components all of which have been purified to homogeneity (Shorr et al., 1982; Homcy et al., 1983; Benovic et al., 1984; Codina et al., 1984; Northup et al., 1980; Sternweis et al., 1981; Bokoch et al., 1984; Pfeuffer et al., 1985). Initially, agonist binding to the receptor promotes coupling of the occupied receptor to one of the guanine nucleotide binding regulatory proteins. These proteins are members of a family of heterotrimeric proteins consisting of alpha, beta and gamma subunits. Stimulatory receptors like the beta-adrenergic (Cerione et al., 1984) or glucagon (Iyengar et al., 1979) receptors couple to the stimulatory regulatory protein Ns (or Gs) whereas inhibitory receptors like the alpha 2-adrenergic (Jacobs et al., 1976) or M2-muscarinic (Harden et al., 1982) receptors couple to the inhibitory regulatory protein Ni (or Gi). Prolonged exposure to agonist hormones, either stimulatory or inhibitory, results in an attenuation of the response to the hormonal activation, a phenomenon called tachyphylaxis or desensitization (Harden, 1983; Sibley and Lefkowitz, 1985; Sharma et al., 1975). One of the best studied models for desensitization is the beta-adrenergic receptor-coupled adenylate cyclase system. In this system two different forms of desensitization have been characterized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells. 284 12

Chick hepatocytes in primary culture have been used to study the homologous and heterologous pathways of glucagon-induced desensitization of adenylyl cyclase. Scatchard analysis and guanine nucleotide effects on dissociation kinetics indicate that the initial phase of homologous desensitization, an increase in low affinity glucagon receptors due to the rapid uncoupling of the receptor from Gs, is essentially complete within 5 min. These receptors recouple within 20 min upon removal of glucagon. Upon prolonged (2 h or more) exposure of hepatocytes to glucagon, disappearance of low affinity receptors from cell surface membranes constitutes the second phase of homologous desensitization. Recovery of these lost and presumably internalized receptors requires more than 12 h following the removal of glucagon but is not dependent on new protein synthesis. The heterologous phase of desensitization is slower, requiring 20-30 min of glucagon treatment to reach completion. Stimulation of adenylyl cyclase by hormonal and nonhormonal effectors is similarly reduced, indicating a common defect in this desensitized state. Agonist occupancy of other hormone receptors coupled to adenylyl cyclase in hepatocytes, such as beta-adrenergic, prostaglandin E1, and vasoactive intestinal peptide, results in heterologous desensitization. Heterologous desensitization is rapidly reversed (within 30 min) upon partial removal of glucagon, under conditions allowing the maintenance of the homologously desensitized state. Neither onset of nor recovery from heterologous desensitization requires protein synthesis. These data indicate that homologous and heterologous desensitization occurs by independent mechanisms. Homologous desensitization involves uncoupling of the glucagon receptor from Gs, followed by removal of these uncoupled receptors from the cell surface. Heterologous desensitization represents a second level of cellular control of hormonal responsiveness to be turned on when the cell is subjected to prolonged hormonal stimulation and withdrawn when hormone levels are lowered.
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PMID:Glucagon-induced desensitization of adenylyl cyclase in primary cultures of chick hepatocytes. Evidence for multiple pathways. 284 35

Four subclones of the originally cloned Harvey murine sarcoma virus-transformed Madin Darby canine kidney (MDCK) cells have been isolated. These subclones fall into two general classes. Two subclones have a fibroblastic morphology, have lost the growth requirement for prostaglandin E1 (PGE1), do not respond to glucagon or vasopressin, and, in general, appear transformed. Two other subclones have epithelioid morphologies, are growth-stimulated by PGE1, respond to vasopressin with an increase in intracellular cAMP. We propose that these cells represent revertants to a more non-transformed phenotype. Unlike normal cells, however, these revertants grow under anchorage-independent conditions, express detectable but reduced amounts of the transforming gene product, p21, and grow in nude mice. The appearance of such revertants may be one cause of the observed heterogeneity of tumor cells.
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PMID:Revertants of Ha-MuSV-transformed MDCK cells express reduced levels of p21 and possess a more normal phenotype. 300 21


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