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)

Plasmids containing cDNAs encoding either the wild-type guanine-nucleotide-binding protein G(o)1 alpha or the palmitoylation-negative cysteine-3-to-serine (C3S) mutant of G(o)1 alpha were transfected into Rat 1 cells, and clones stably expressing immunoreactivity corresponding to these polypeptides were isolated. Clones C5B (expressing wild-type G(o)1 alpha) and D3 (expressing the mutant form) were selected for detailed study. Immunoprecipitation of whole cell lysates of each clone labelled with either [3H]palmitate or [3H]myristate demonstrated incorporation of [3H]myristate into both wild-type and the C3S mutant of G(o)1 alpha, but that incorporation of hydroxylamine-sensitive [3H]palmitate was restricted to the wild type. When membrane and cytoplasmic fractions were prepared from cells of either the C5B or D3 clones, although immunodetection of wild-type G(o)1 alpha was observed only in the membrane fraction, the C3S mutant was present in both membrane and cytoplasmic fractions. Furthermore, a significant proportion of the C3S G(o)1 alpha immunoreactivity was also detected in the cytoplasmic fraction if immunoprecipitation of recently synthesized G(o)1 alpha was performed from fractions derived from cells pulse-labelled with [35S]Trans label. Pretreatment of cells of both clones C5B and D3 with pertussis toxin led to complete ADP-ribosylation of the cellular population of G(o)1 alpha in both cell types, irrespective of whether the polypeptide was subsequently found in the membrane or cytoplasmic fraction following cellular disruption. By contrast, separation of membrane and cytoplasmic fractions before pertussis-toxin-catalysed [32P]ADP-ribosylation allowed modification only of the membrane-associated G(o)1 alpha (whether wild-type or the C3S mutant). This labelling was decreased substantially by incubation of the membranes with guanosine 5'-[beta gamma-imido]triphosphate. No cytoplasmic G-protein beta subunit was detected immunologically, and the non-membrane-associated C3S G(o)1 alpha from D3 cells migrated as an apparently monomeric 40 kDa protein on a Superose 12 gel-filtration column. Membrane-associated wild-type and C3S G(o)1 alpha appeared to interact with guanine nucleotides with similar affinity, as no alteration in the dose-response curves for guanine-nucleotide-induced maintenance of a stable 37 kDa tryptic fragment was noted for the two forms of G(o)1 alpha. Chemical depalmitoylation of membranes of clone C5B with neutral 1 M hydroxylamine caused a release of some 25-30% of each of G(o)1 alpha, Gi2 alpha and Gq alpha/G11 alpha from the membranes. Equivalent treatment of D3 cells caused an equivalent release of Gi2 alpha and Gq alpha/G11 alpha, but was unable to cause any appreciable release of the CS3 form of G(o)1 alpha, which was membrane-bound.
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PMID:The palmitoylation status of the G-protein G(o)1 alpha regulates its activity of interaction with the plasma membrane. 794 20

In neuroblastoma-glioma hybrid cells, bradykinin has dual modulatory effects on ion channels: it activates a K+ current as well as inhibits the voltage-dependent Ca2+ current (ICa,V). Both of these actions are mediated by pertussis toxin-insensitive G proteins. Antibodies raised against the homologous Gq and G11 proteins suppress only the activation of the K+ current; this suggested that at least two distinct G protein pathways transduce diverse effects of this transmitter. Here, we show that the inhibition of ICa,V by bradykinin is suppressed selectively by intracellular application of antibodies specific for G13. This novel G protein may play a general role in the inhibition of ICa,V by pathways resistant to pertussis toxin.
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PMID:The G protein G13 mediates inhibition of voltage-dependent calcium current by bradykinin. 794 58

Previously, we have shown that myocytes from rat portal vein express alpha 1A-adrenoreceptors that couple with a Gq/G11-protein to stimulate phosphoinositide turnover and release of calcium from intracellular stores. The purpose of this study was to investigate the contribution of both alpha 1- and alpha 2-adrenoreceptor subtypes in inducing stimulation of voltage-operated calcium channels. Norepinephrine (a nonselective alpha-adrenoreceptor agonist), phenylephrine (an alpha 1-adrenoreceptor agonist), clonidine, and oxymetazoline (alpha 2-adrenoreceptor agonists) stimulated the calcium channel current by a similar extent. Using subtype-selective antagonists we showed that both alpha 1A- and alpha 2A-adrenoreceptors modulated voltage-operated calcium channels through two distinct transduction pathways. alpha 1A-Adrenoreceptors coupled with a pertussis toxin-insensitive G-protein whereas alpha 2A-adrenoreceptors coupled with a pertussis toxin-sensitive G-protein. Portal vein myocytes expressed G-proteins that were recognized by anti-alpha q/alpha 11, -alpha i(1-2), and -alpha i(3) antibodies. As internal applications of anti-phosphatidylinositol and anti-alpha q/alpha 11 antibodies had no effect on the alpha 2A-adrenoreceptor-induced enhancement of calcium channel current, these findings suggest that phosphatidylinositol hydrolysis and Gq/G11-protein are not involved in the alpha 2A-adrenoreceptor-induced coupling process. A protein kinase C inhibitor, GF 109203X, and a long term (24 h) treatment with phorbol dibutyrate to decrease the activity of protein kinase C blocked the alpha 1A- and alpha 2A-adrenoreceptor-induced stimulation of calcium channels as well as that stimulation induced by phorbol dibutyrate. Moreover, activation of alpha 2A-adrenoreceptors did not induce a significant calcium release from intracellular stores. These data suggest that two distinct G-proteins, probably Gq/G11 and Gi, coupled to alpha 1A- and alpha 2A-adrenoreceptors regulate calcium influx through voltage-operated calcium channels by two different transduction pathways leading to activation of protein kinase C.
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PMID:Both alpha 1A- and alpha 2A-adrenoreceptor subtypes stimulate voltage-operated L-type calcium channels in rat portal vein myocytes. Evidence for two distinct transduction pathways. 796 39

Various mechanisms have been identified by which hormones and neurotransmitters, interacting with heptahelical receptors, modulate the intracellular Ca2+ concentration in neuronal, endocrine, and neuroendocrine cells. All of them involve heterotrimeric G proteins. Best documented are hormonal stimulations and inhibitions of voltage-dependent Ca2+ channels. Stimulation is caused by agonists interacting with receptors known to induce phosphatidylinositol 4,5-bisphosphate hydrolysis, that is, a PI response. Although the PI response triggers a transient secretion by fast Ca2+ release, the stimulation of Ca2+ channels is assumed to be responsible for prolonged cell responses and for refilling of IP3-sensitive Ca2+ pools after repeated stimulations. Using antisense oligonucleotide microinjection in rat pituitary GH3 cells, Gi2 has been identified as the pertussis toxin-sensitive G protein stimulating Ca2+ channels, whereas Gq/G11 are involved in the concurrent PI response with subsequent protein kinase C activation, which is required for Ca2+ channel stimulation. Inhibitory modulations of Ca2+ channels are assumed to be the basis of inhibitions of transmitter or hormone secretion. Experiments in GH3 cells have revealed that Go subforms composed of alpha o1 x beta 3 x gamma 4 and alpha o2 x beta 1 x gamma 3 are the active G-protein heterotrimers transferring inhibitory signals from muscarinic M4 and somatostatin receptors to the Ca2+ channel, respectively.
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PMID:Heterotrimeric G proteins involved in the modulation of voltage-dependent calcium channels of neuroendocrine cells. 797 80

Xenopus oocytes were used to examine the coupling of the serotonin 1c (5HT1c) and thyrotropin-releasing hormone (TRH) receptors to both endogenous and heterologously expressed G protein alpha subunits. Expression of either G protein-coupled receptor resulted in agonist-induced, Ca(2+)-activated Cl- currents that were measured using a two-electrode voltage clamp. 5HT-induced Cl- currents were reduced 80% by incubating the injected oocytes with pertussis toxin (PTX) and inhibited 50-65% by injection of antisense oligonucleotides to the PTX-sensitive Go alpha subunit. TRH-induced Cl- currents were reduced only 20% by PTX treatment but were inhibited 60% by injection of antisense oligonucleotides to the PTX-insensitive Gq alpha subunit. Injection of antisense oligonucleotides to a novel Xenopus phospholipase C-beta inhibited the 5HT1c (and Go)-induced Cl- current with little effect on the TRH (and Gq)-induced current. These results suggest that receptor-activated Go and Gq interact with different effectors, most likely different isoforms of phospholipase C-beta. Co-expression of each receptor with seven different mammalian G protein alpha subunit cRNAs (Goa, Gob, Gq, G11, Gs, Golf, and Gt) was also examined. Co-expression of either receptor with the first four of these G alpha subunits resulted in a maximum 4-6-fold increase in Cl- currents; the increase depended on the amount of G alpha subunit cRNA injected. This increase was blocked by PTX for G alpha oa and G alpha ob co-expression but not for G alpha q or G alpha 11 co-expression. Co-expression of either receptor with Gs, Golf, or Gt had no effect on Ca(2+)-activated Cl- currents; furthermore, co-expression with Gs or Golf also failed to reveal 5HT- or TRH-induced changes in adenylyl cyclase as assessed by activation of the cystic fibrosis transmembrane conductance regulator Cl- channel. These results indicate that in oocytes, the 5HT1c and TRH receptors do the following: 1) preferentially couple to PTX-sensitive (Go) and PTX-insensitive (Gq) G proteins and that these G proteins act on different effectors, 2) couple within the same cell type to several different heterologously expressed G protein alpha subunits to activate the oocyte's endogenous Cl- current, and 3) fail to couple to G protein alpha subunits that activate cAMP or phosphodiesterase.
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PMID:Differential coupling of G protein alpha subunits to seven-helix receptors expressed in Xenopus oocytes. 798 22

In the present work we have investigated the effects of several growth factors on the expression of Angiotensin II (A-II) receptors subtype AT1 and their pertussis toxin-insensitive coupling to G-proteins in bovine adrenal fasciculata-reticularis cells (BAC). Insulin, Insulin-like growth factor and basic Fibroblast growth factor increased AT1 receptors (mRNA and binding sites) as well as the alpha subunit of Gq (mRNA and protein) and G11 (protein). These changes were associated with an enhanced A-II-induced inositol phosphate accumulation and cortisol production. In contrast, Transforming growth factor beta 1, which reduced slightly AT1 binding sites, but not the level of alpha q or alpha 11 proteins, did not change the A-II-induced inositol phosphate accumulation. However, this factor, as previously reported, markedly reduced cortisol production.
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PMID:Regulation by growth factors of angiotensin II type-1 receptor and the alpha subunit of Gq and G11 in bovine adrenal cells. 801 89

Acetylcholine (ACh)-induced contraction of esophageal circular smooth muscle cells was inhibited by the M2 muscarinic antagonist methoctramine. In lower esophageal sphincter (LES) cells contraction was inhibited by the M3 antagonist p-fluoro-hexa-hydro-sila-difenidol (pF-HSD). Pertussis toxin (PTX) reduced ACh-induced contraction of esophageal but not of LES cells, which suggested that different receptor-linked G proteins are involved. Antibodies against G13 antagonized contraction of esophageal cells and G9-G11 antibodies antagonized contraction of LES cells. The phosphatidylinositol-specific phospholipase C (PLC) inhibitors, U-73122 and neomycin, reduced ACh-induced contraction of LES but not of esophageal cells. Conversely, propranolol and p-chloromercuribenzoic acid (pCMB), which inhibit a phosphatidylcholine-specific phospholipase D (PLD)-dependent pathway, reduced contraction of esophageal but not of LES muscle cells. At 1 and 5 sec after the administration of ACh (10(-5) M), inositol 1,4,5-trisphosphate (IP3) increased only in LES muscle, which suggested that contraction results from PLC-induced IP3 production in the LES but not in the esophagus. The IP3 receptor antagonist heparin, and depletion of intracellular Ca++ stores by thapsigargin or A23187, inhibited ACh-induced contraction of LES but not of esophageal muscle. It was concluded that ACh-induced esophageal contraction depends preferentially on M2 receptors, a PTX-sensitive G13 protein, phosphatidylcholine-specific PLD and production of diacylglycerol (DAG) and is independent of IP3 formation and the release of intracellular Ca++. Conversely, LES contraction is mediated through M3 receptors, a PTX-insensitive G9-G11 protein, activation of PLC, IP3 formation and the release of intracellular Ca++.
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PMID:Distinct muscarinic receptors, G proteins and phospholipases in esophageal and lower esophageal sphincter circular muscle. 826 81

In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to IK,BK, through activation of a calcium-dependent potassium current. In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins. Here, we have investigated the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and occluded both actions of BK, and both effects were insensitive to pertussis toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin-insensitive G protein.
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PMID:Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. 829 55

In rat pituitary GH3 cells, thyrotropin-releasing hormone (TRH) and other secretion-stimulating hormones trigger an increase in the cytosolic Ca2+ concentration by two mechanisms. Ca2+ is released from intracellular stores in response to inositol 1,4,5-trisphosphate and can enter the cell through voltage-dependent L-type Ca2+ channels. Stimulation of these channels is sensitive to pertussis toxin, indicating that a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding regulatory protein (G protein) is involved in functional coupling of the receptor to the Ca2+ channel. We identified the G protein involved in the stimulatory effect of TRH on the Ca2+ channel by type-selective suppression of G-protein synthesis. Antisense oligonucleotides were microinjected into GH3 cell nuclei, and 48 h after injection the TRH effect was tested. Whereas antisense oligonucleotides hybridizing to the mRNA of G(o) or Gi1 alpha-subunit sequences did not affect stimulation by TRH, oligonucleotides suppressing the expression of the Gi2 alpha subunit abolished this effect, and oligonucleotides directed against the mRNA of the Gi3 alpha subunit had less effect. The requirement of a concurrent inositol phospholipid degradation and subsequent protein kinase C (PKC) activation for the TRH effect on Ca(2+)-channel activity was demonstrated by inhibitory effects of antisense oligonucleotides directed against Gq/G11/Gz alpha-subunit sequences and treatment of GH3 cells with PKC inhibitors, respectively. Our results suggest that TRH elevates the cytosolic Ca2+ concentration in GH3 cells transiently via Ca2+ release from internal stores, followed by a phase of sustained Ca2+ influx through voltage-dependent Ca2+ channels stimulated by the concerted action of Gi2 (and Gi3) plus PKC.
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PMID:Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. 839 94

The pertussis toxin-insensitive G proteins that stimulate phosphoinositide phospholipase C consist of 42- and 43-kDa alpha-subunits, 35-kDa beta-subunits and 8-kDa gamma-subunits. The alpha-subunits have been identified as alpha q and alpha 11, and both specifically stimulate the beta 1 isozyme of the phospholipase. Activation of Ca(2+)-mobilizing receptors in liver plasma membranes selectively induces the labelling of alpha q and alpha 11 by [alpha-32P]GTP-azidoanilide. Reconstitution of Gq and G11 with M1 muscarinic receptor and the beta 1 isozyme allows GTP gamma S-dependent stimulation of PtdInsP2 hydrolysis by carbachol. These data establish unequivocally that Gq and G11 function as the transducing G proteins for Ca(2+)-mobilizing receptors.
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PMID:Role of G proteins in activation of phosphoinositide phospholipase C. 839 19


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