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)

The coupling of two endothelin receptor subtypes (ET(A) and ETB) to several types of guanine-nucleotide-binding regulatory protein (G protein) was examined. Two subtypes of receptor cDNAs were transfected alone or together with four different G protein alpha subunit cDNAs in COS-7 cells. In ET(A) receptor-transfected cells, endothelin-1 (ET-1) activated phosphatidylinositol-specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. ETB-receptor-transfected cells also produced Ins(1,4,5)P3 on stimulation by ET-1. The ET-1-induced production of Ins(1,4,5)P3 was markedly higher in G alpha q-cotransfected or G alpha 11-cotransfected cells than in cells transfected with each receptor alone. ET-1 also stimulated production of cAMP in ET(A) or ETB receptor-transfected cells. The production of cAMP was synergistically amplified by G alpha s co-transfection with each receptor. In contrast, when G alpha i2 was co-transfected with the ET(A) or ETB receptor, ET-1 displayed an inhibitory action on forskolin-stimulated cAMP accumulation. Pertussis-toxin treatment of the G alpha i2-transfected cells resulted in abolition of the endothelin-induced inhibition of cAMP accumulation. These observations indicate that both ET(A) and ETB receptors are able to couple to Gq, G11, Gs and Gi2, and suggest that endothelin receptors stimulate multiple effectors via several types of G protein simultaneously. The overall effects induced by endothelin may differ in cell types depending on the level of expression of each G-protein subtype in the cell.
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PMID:Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. 788 89

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

1. Rat cultured ventromedial hypothalamic (VMH) neurones obtained from embryonic hypothalamus were used to study the muscarinic (carbachol) modulation of voltage-gated K+ currents with the whole-cell patch-clamp technique. 2. Carbachol produced a potent and concentration-dependent (100 fM to 100 microM) decrease of the outward delayed rectifier K+ current (IK) with an IC50 of 44 pM and a Hill coefficient of 0.4. The carbachol-induced depression of IK was reduced by pirenzepine (1-10 microM) and atropine (1 microM). Carbachol had no effect on the transient outward K+ current (IA). 3. Intracellular dialysis with guanosine 5'-O-(2-thiodiophosphate) (GDP-beta-S, 500 microM) significantly diminished the carbachol-induced depression of IK, suggesting GTP-binding protein (G-protein) involvement. Pre-incubation of VMH neurones with pertussis toxin (200-400 ng ml-1) or cholera toxin (1 microgram ml-1) for 24-48 h had no effect on the carbachol-induced depression of IK. This suggested that the G alpha o, G alpha i, and G alpha s G-protein alpha-subunits were not involved in mediating the carbachol-induced depression of IK in VMH neurones. 4. Treatment (24-48 h) of VMH neurones with antisense phosphothio-oligodeoxynucleotides to the G alpha 11 G-protein subunit (10 microM) significantly diminished the carbachol-induced depression of IK. Treatment with 10 microM of either G alpha 11 sense or antisense to G alpha q had no effect. 5. These results demonstrate a novel and potent muscarinic depression of IK in VMN neurones, and that this depression is specifically mediated by the G alpha 11 G-protein subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarine modulation by a G-protein alpha-subunit of delayed rectifier K+ current in rat ventromedial hypothalamic neurones. 801 94

We examined the types of guanine nucleotide-binding regulatory (G) protein subunits in isolated glomeruli, cortices excluding glomeruli and medullas of rat kidneys using bacterial toxin-catalyzed adenosine 5'-diphosphate (ADP) ribosylation and specific immunoblots. ADP ribosylation catalyzed by cholera or pertussis toxin revealed the presence of stimulatory G (Gs) or inhibitory G (Gi) proteins in membranes of the 3 segments of the kidney. Immunoblots further demonstrated the existence of several G-protein subunits, two Gs-protein alpha-subunits (G alpha s: 45 and 52 kD), Gi-protein alpha 1, alpha 2 and alpha 3-subunits (G alpha i1, G alpha i2: 40-41 kD, G alpha i3: 40 kD), bacterial toxin-insensitive G-protein alpha q- and alpha 11-subunits (G alpha q/11: 42 kD) and G-protein beta-subunits (G beta: 35-36 kD), in membranes of the preparations. The predominant subspecies of G alpha s was a 52-kD protein in glomerular membranes and a 45-kD protein in membranes of cortices and medullas. All of the G-protein subunits examined, however, were not detected in cytosolic fractions of glomeruli, cortices and medullas. Thus, we conclude that detectable quantities of several G-protein subunits including the new G-protein subunit, G alpha q/11, are present in membranes of glomeruli, cortices not containing glomeruli and medullas from the rat kidney. Both the existence of G alpha i1 and/or G alpha i2 subunits in glomeruli and the presence of G alpha q/11 subunits in the 3 preparations are new evidence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional characterization of G-protein subunits in glomeruli, cortices and medullas of the rat kidney. 801 50

Bradykinin stimulates diverse functions in endothelial cells including the release of endothelium-derived relaxing factor (EDRF). Little is known, however, regarding the identity of the G protein(s) involved. Here we demonstrate that G proteins of the G alpha i and G alpha q family are coupled to the bradykinin receptor (BKR) in bovine aortic endothelial cells by using specific antisera directed against the COOH-terminal region of G alpha i2 (P4), G alpha i3 (EC), and G alpha q (QL). These antisera are specific since their effects are blocked by the decapeptides from which they were derived. The degree of receptor-G protein coupling was assessed by the formation of high affinity agonist binding sites (HABS) and GTP hydrolysis. In a concentration-dependent manner, the QL antisera reduced HABS and GTPase activity by 65 and 60%, respectively, and effectively abolished them in membranes from pertussis toxin-treated cells. The combination of P4 and EC antisera produced a loss of HABS (41%) and GTPase activity (40%) comparable to the effects of pertussis toxin. These findings indicate that G alpha i and G alpha q proteins mediate the cellular responses to bradykinin in bovine aortic endothelial cells and support the observation that bradykinin-stimulated EDRF release is relatively insensitive to pertussis toxin.
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PMID:The G proteins of the G alpha i and G alpha q family couple the bradykinin receptor to the release of endothelium-derived relaxing factor. 822 32

In bovine aortic endothelial cells (BAEC), pertussis toxin (PTx) ADP-ribosylated two major substrates with apparent molecular masses of 40 and 41 kDa, whereas cholera toxin (CTx) ADP-ribosylated two other substrates of 44 and 50 kDa. [alpha-32P]GTP bound to three bands in the 22-27 kDa range. Immunoblot analysis revealed the simultaneous presence of G alpha i1, G alpha i2, G alpha i3, G alpha q or G alpha 11 and of different forms of G alpha s but did not detect significant levels of G alpha 0. Bradykinin caused a 9-fold increase in intracellular cyclic GMP level in BAEC (measured as an index of NO production). Preincubation of BAEC with CTx, but not with PTx, inhibited bradykinin-dependent production of cyclic GMP. These results show that G alpha s, G alpha q or alpha 11, Gi and small GTP-binding proteins are present in BAEC and suggest that a CTx-sensitive G-protein (possibly either small G-protein, G alpha q or G alpha 11) could be associated with the bradykinin-mediated NO formation.
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PMID:G proteins in aortic endothelial cells and bradykinin-induced formation of nitric oxide. 828

Receptor activation of phospholipase C (PLC) via G-proteins occurs by pertussis toxin-sensitive and toxin-insensitive signaling pathways. The alpha-subunits of the Gq family are presumed to mediate the toxin-insensitive pathway, but the nature of the G-proteins mediating the toxin-sensitive pathway is not established. Recently, PLC-beta has been shown to be activated by G-protein beta gamma-subunits of mixed or undefined composition. The relative activities of G-protein subunits that might activate PLC-beta were examined using defined recombinant alpha- and beta gamma-subunits obtained from the baculovirus expression system by reconstituting the purified subunits with purified bovine brain PLC-beta 1 or turkey erythrocyte PLC-beta in unilamellar phospholipid vesicles. Turkey erythrocyte G alpha 11 and recombinant G alpha 11 and G alpha q obtained after expression in Sf9 cells activated both bovine brain PLC-beta 1 and turkey erythrocyte PLC-beta. In contrast, under the same assay conditions, recombinant G alpha i1, G alpha i2, G alpha i3, and G alpha o were without effect on either type of PLC. All types of beta gamma-subunits tested (r beta 1 gamma 2, r beta 1 gamma 3, r beta 2 gamma 2, r beta 2 gamma 3, bovine brain beta gamma or turkey erythrocyte beta gamma) inhibited G alpha 11-mediated activation of PLC, presumably by promotion of formation of inactive heterotrimeric G-protein. All types of beta gamma-subunits also markedly stimulated the activity of turkey erythrocyte PLC-beta but did not activate bovine brain PLC-beta 1. Of the four different beta gamma complexes of defined composition, three stimulated PLC with similar activities whereas beta 2 gamma 3 was less effective. The data suggest that pertussis toxin-sensitive activation of PLC is mediated by the beta gamma-subunits of G-proteins acting on specific phospholipase C isoenzymes.
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PMID:Selective activation of phospholipase C by recombinant G-protein alpha- and beta gamma-subunits. 830 Jun 14

Interleukin-8 (IL-8) is one of the major mediators of the inflammatory response. The pathways by which IL-8 activates inositide-specific phospholipase C (PLC) were investigated by co-expression of different components of the guanosine triphosphate binding protein (G protein) pathway in COS-7 cells. Two distinct IL-8 receptors reconstituted ligand-dependent activation of endogenous PLC when transfected together with the G protein alpha subunits G alpha 14, G alpha 15, or G alpha 16. However, reconstitution was not observed with cells that overexpressed G alpha q or G alpha 11. Furthermore, IL-8 receptors interacted with endogenous pertussis toxin-sensitive G proteins or with the recombinant G protein Gi to release free beta gamma subunits that could then specifically activate the beta 2 isoform of PLC. These findings suggest that IL-8 acts through signal-transducing pathways that are limited to specific heterotrimeric G proteins and effectors. These may provide suitable targets for the development of anti-inflammatory agents.
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PMID:G protein-coupled signal transduction pathways for interleukin-8. 831 40

A newly identified subclass of the heterotrimeric GTP binding regulatory protein family, Gq, has been found to be expressed in a diverse range of cell types. We investigated the potential role of this protein in growth factor signal transduction pathways and its potential relationship to the function of other G alpha subclasses. Recent biochemical studies have suggested that Gq regulates the beta 1 isozyme of phospholipase C (PLC beta 1), an effector for some growth factors. By microinjection of inhibitory antibodies specific to distinct G alpha subunits into living cells, we have determined that G alpha q transduces bradykinin- and thrombin-stimulated intracellular calcium transients which are likely to be mediated by PLC beta 1. Moreover, we found that G alpha q function is required for the mitogenic action of both of these growth factors. These results indicate that both thrombin and bradykinin utilize Gq to couple to increases in intracellular calcium, and that Gq is a necessary component of the mitogenic action of these factors. While microinjection of antibodies against G alpha i2 did not abolish calcium transients stimulated by either of these factors, such microinjection prevented DNA synthesis in response to thrombin but not to bradykinin. These data suggest that thrombin-induced mitogenesis requires both Gq and Gi2, whereas bradykinin needs only the former. Thus, different growth factors operating upon the same cell type use overlapping yet distinct sets of G alpha subtypes in mitogenic signal transduction pathways. The direct identification of the coupling of both a pertussis toxin sensitive and insensitive G protein subtype in the mitogenic pathways utilized by thrombin offers an in vivo biochemical clarification of previous results obtained by pharmacologic studies.
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PMID:Mediation of growth factor induced DNA synthesis and calcium mobilization by Gq and Gi2. 845 76

To evaluate the effects of bilateral ureteral obstruction (BUO) on the levels of G-protein subunits in glomeruli, we examined the types and amounts of G-protein subunits in glomerular membranes from sham-operated control (SOC) rats and rats with BUO of 24 hours duration utilizing bacterial toxin-catalyzed ADP-ribosylation and specific antibodies. ADP-ribosylation catalyzed by cholera or pertussis toxin demonstrated the presence of Gs and Gi proteins in glomerular membranes. Immunoblots further revealed the existence of two types of G alpha s (45 and 52 kDa), as well as G alpha i2 (40 kDa), G alpha i3 (41 kDa), G alpha q/11 (42 kDa) and G beta (35 to 36 kDa) in glomerular membranes. The predominant subspecies of G alpha s was the 52 kDa protein. Detectable amounts of G alpha o were not found in glomerular membranes. Moreover, G-protein subunits were not detected in cytosolic extracts of glomeruli. Both forms of G alpha s and G alpha q/11 were significantly reduced in glomerular membranes from rats with BUO when compared to SOC rats. No significant difference in total G alpha i, G alpha i2 and G alpha i3 and G beta content was observed between the two groups of rats. In vivo pretreatment of rats with simultaneous administration of the angiotensin-converting enzyme inhibitor, enalaprilat, and the thromboxane synthase inhibitor, OKY-046, maintained the amount of G alpha s and G alpha q/11 in rats with BUO at the levels seen in SOC rats. The two drugs did not affect the amounts of G-protein subunits in glomerular membranes of SOC rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bilateral ureteral obstruction alters levels of the G-protein subunits G alpha s and G alpha q/11. 847 22


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