Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary growth hormone (GH) functions physiologically to oppose the actions of insulin on carbohydrate and lipid metabolism by interfering with metabolic events that occur after insulin binds to its receptor. Which postreceptor effects are involved is presently unknown. Recently, we found that insulin rapidly stimulates a phosphatidylinositol phospholipase C (PI-PLC) in adipose tissue of obese (ob/ob) mice and that this effect of insulin is blocked by treatment of the animals with S-carboxymethylated human GH (RCM-hGH), a derivative having mainly anti-insulin activity. The activation of this PI-PLC by insulin is also inhibited by pertussis toxin. Thus, this study was performed to examine whether the inhibitory effect of GH on the activation of this PI-PLC is exerted at the level of signal transmission by guanine nucleotide binding proteins (G proteins). We found that the nonhydrolyzable GTP analogue, guanosine 5'-[gamma-thio]triphosphate, stimulated basal PI-PLC activity in plasma membranes of adipose tissue of saline-treated ob/ob mice, but it did not stimulate the enzyme in adipose membranes from RCM-hGH-treated mice. Also, RCM-hGH treatment markedly inhibited pertussis toxin-catalyzed ADP ribosylation of G protein alpha subunits in the membranes, suggesting some modification of the G proteins by GH. Immunoblot analysis of adipose membranes from saline- and RCM-hGH-treated mice using antiserum AS/7 (anti-Gi1 alpha and anti-Gi2 alpha) or antiserum EC/2 (anti-Gi3 alpha) showed no difference in the amount of Gi alpha-like protein between the groups. These findings suggest that GH interferes with the ability of a putative Gi-like protein to mediate the activation of PI-PLC in adipose membranes without altering the expression of the G protein.
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PMID:Growth hormone inhibits activation of phosphatidylinositol phospholipase C in adipose plasma membranes: evidence for a growth hormone-induced change in G protein function. 184 8

1. Growth hormone (GH) secretion from the anterior pituitary gland is mainly regulated by hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIF). Somatostatin reduces both spontaneous and GHRH-stimulated GH secretion. 2. Exocytosis of GH is mainly determined by the intracellular free Ca2+ concentration ([Ca2+]i), which is regulated by the influx of Ca2+ via membrane Ca2+ channels. Somatostatin reduces the influx of Ca2+ through two separate mechanisms, namely a direct action on Ca2+ channels and an indirect action on membrane potentials through the activation of K+ channels. 3. In the present experiments, somatotroph-enriched cells were obtained from the ovine pituitary gland by means of collagenase dissociation and Percoll-gradient centrifugation. Further identification was based on the effect of SRIF (10 nmol/L) on Ca2+ or K+ currents. 4. A significant reduction in Ca2+ currents and an increase in K+ currents was obtained in response to local application of SRIF (10 nmol/L), but vehicle application had no effect. The responses of Ca2+ and K+ currents to SRIF were reversible after removal of SRIF. 5. Dialysis of GTP-gamma-s (200 mumol/L) abolished the recovery phase of K+ current response to SRIF after its removal, whereas GDP-beta-s (200 mumol/L) totally blocked the response. Pretreatment of the cells with pertussis toxin (100 nmol/L) overnight abolished the Ca2+ current response to SRIF. 6. Intracellular dialysis of antibodies to alpha o, alpha i1-3, alpha i1-2 and alpha i3 subunits of the G-proteins into cells via whole-cell patch-clamp pipettes was confirmed by immunofluorescent staining of the antibodies. 7. Dialysis of anti-alpha i1-3 or anti-alpha i3 antibodies significantly attenuated the increase in the K+ current in response to 10 nmol/L SRIF, whereas neither anti-alpha o nor anti-alpha i1-2 antibodies diminished the effect of SRIF on the K+ current. 8. Dialysis of anti-alpha o antibodies significantly attenuated the reduction in the Ca2+ current that was obtained upon application of 10 nmol/L SRIF. Neither anti-alpha i1-2 nor anti-alpha i3 antibody dialysis diminished the effect of SRIF on the Ca2+ current. 9. Dialysis of the alpha o common antisense oligonucleotides (ASm) but not the alpha i3 AS significantly diminished the inhibitory effect of SRIF on the Ca2+ current. This effect of alpha o ASm dialysis occurred at 12 h incubation after dialysis, reaching a maximal level at 48 h and partially recovering at 72 h incubation. Antisense oligonucleotides specific for alpha o1 (alpha o1 AS) or alpha o2 (alpha o2 AS) were dialysed into somatotrophs and only alpha o2 AS significantly attenuated the inhibition of SRIF on the Ca2+ current. 10. It is concluded that the Gi3 protein mediates the effect of SRIF on the K+ current and that the G(o)2 protein mediates the effect of SRIF on the Ca2+ current in primary cultured ovine somatotrophs.
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PMID:G(o)2 and Gi3 proteins mediate the action of somatostatin on membrane Ca2+ and K+ currents in ovine pituitary somatotrophs. 926 41

Growth hormone (GH) is an important mitogenic stimulus for the insulin-producing beta-cell. We investigated the effects of GH on Ca(2+) handling and diacylglycerol (DAG) and cAMP formation in the beta-cell. GH elicited a rapid increase in the cytoplasmic free [Ca(2+)], which required extracellular Ca(2+) and was also blocked by pertussis toxin or protein kinase C (PKC) inhibition. GH also elevated islet DAG content, which should lead to PKC activation. Pertussis toxin and PKC inhibitors obliterated the mitogenicity of GH, suggesting involvement of GTP-binding proteins. PKC activation stimulated beta-cell proliferation, and it also activated phospholipase D. Islet cAMP content was not elevated by GH. Addition of a specific protein kinase A antagonist failed to influence the mitogenicity of GH, whereas a stimulatory cAMP agonist stimulated beta-cell replication. We conclude that GH rapidly increases the beta-cell cytoplasmic free [Ca(2+)] and also evokes a similar increase in DAG content via a phosphatidylcholine-specific phospholipase C, but does not affect mitogen-activated protein kinases, phospholipase D, or the cAMP signaling pathway. This rise in DAG may be of importance in translation of the stimulatory signal of GH into a proliferative response by the beta-cell, which seems to occur through GTP-binding proteins and PKC-dependent mechanisms.
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PMID:Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone-mediated islet beta -cell mitogenesis. 1074

Growth hormone (GH) secretion is regulated by indirect negative feedback mechanisms. To address whether GH has direct actions on pituitary cells, lipid signaling in GH(4)ZR(7) somatomammotroph cells was examined. GH (EC(50) = 5 nm) stimulated diacylglycerol (DAG) and ceramide formation in parallel by over 10-fold within 15 min and persisting for >3 h. GH-induced DAG/ceramide formation was blocked by pertussis toxin (PTX) implicating G(i)/G(o) proteins and was potentiated 1.5-fold by activation of G(i)/G(o)-coupled dopamine-D2S receptors, which had no effect alone. Following PTX pretreatment, only PTX-resistant Galpha(i)3, not Galpha(o) or Galpha(i)2, rescued GH-induced DAG/ceramide signaling. GH-induced DAG/ceramide formation was also blocked in cells expressing Gbetagamma blocker GRK-ct. In GH(4)ZR(7) cells, GH induced phosphorylation of JAK2 and STAT5, which was blocked by PTX and mimicked by ceramide analogue C2-ceramide or sphingomyelinase treatment to increase endogenous ceramide. We conclude that in GH(4) pituitary cells, GH induces formation of DAG/ceramide via a novel Galpha(i)3/Gbetagamma-dependent pathway. This novel pathway suggests a mechanism for autocrine feedback regulation by GH of pituitary function.
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PMID:Growth hormone-induced diacylglycerol and ceramide formation via Galpha i3 and Gbeta gamma in GH4 pituitary cells. Potentiation by dopamine-D2 receptor activation. 1237 52