UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G-proteins in rat glomeruli were examined using bacterial toxin-catalyzed ADP-ribosylation and specific immunoblots. ADP-ribosylation catalyzed by cholera and pertussis toxin demonstrated the existence of Gs and Gi proteins in the glomerular membranes. Immunoblots further revealed two types of Gs alpha (45 and 52 kDa), Gi alpha 1 and/or Gi alpha 2 (40-41 kDa), Gi alpha 3 (40 kDa) and G beta (35-36 kDa) but not Go alpha in the membranes of the glomeruli. The predominant subspecies of Gs alpha was a 52 kDa protein. However, detectable amounts of G-proteins did not exist in cytosolic extracts of the glomeruli. We conclude that several subspecies of Gs and Gi proteins are present in rat glomerular membranes.
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PMID:Characterization of G-proteins in rat glomeruli. 163 79

In the rat pituitary cell line GH3, carbachol inhibits PRL secretion in a pertussis toxin-sensitive manner. For elucidation of the underlying mechanisms, we studied the effect of carbachol on voltage-dependent Ca2+ currents. Under voltage-clamp conditions, carbachol inhibited whole-cell Ca2+ currents by about 25%. This inhibitory action of carbachol was not observed in cells treated with pertussis toxin, indicating the involvement of a pertussis toxin-sensitive G-protein. In membranes of GH3 cells, carbachol stimulated a pertussis toxin-sensitive high-affinity GTPase. In immunoblot experiments with peptide antisera, we identified two forms of the Gi alpha-subunit (41 and 40 kDa) and two forms of the Go alpha-subunit (40 and 39 kDa). The 40-kDa Gi alpha-subunit was recognized by an antibody specific for the Gi2 alpha-subunit, and the 39-kDa Go alpha-subunit was detected by an antibody specific for the Go2 alpha-subunit. Incubation of membranes with the photoreactive GTP analog [alpha-32P]GTP azidoanilide resulted in photo-labelling of 40- and 39-kDa pertussis toxin substrates comigrating with G-protein alpha-subunits of the corresponding molecular masses. Carbachol dose-dependently stimulated incorporation of the photoreactive GTP analog into the 39-kDa pertussis toxin substrate and, to a lesser extent, into 40-kDa pertussis toxin substrates. The data indicate that muscarinic receptors of GH3 cells couple preferentially to Go, which is likely to be involved in the inhibition of secretion, possibly by conferring an inhibitory effect to voltage-dependent Ca2+ channels.
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PMID:Inhibition of voltage-dependent Ca2+ currents and activation of pertussis toxin-sensitive G-proteins via muscarinic receptors in GH3 cells. 165 34

A new G-protein was detected in human platelets which was ADP-ribosylated in a pertussis-toxin-dependent manner, was located in the supernatant of saponized platelets and was of a slightly lower molecular mass (40 kDa) than platelet membrane Gi alpha. This soluble ADP-ribosylated protein was immunoprecipitated by an antiserum to Gi alpha, but not by one to Go alpha. Prior thrombin stimulation of platelets led to an inhibition of the ADP-ribosylation of this protein. This inhibition was evident even under conditions which abolished the thrombin-stimulated inhibition of membrane Gi alpha ADP-ribosylation. These results indicate that the platelet thrombin receptor is coupled to two structurally and functionally distinct Gi alpha proteins: a major Gi alpha protein present in platelet membranes, and a minor Gi alpha protein detectable in the platelet soluble fraction.
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PMID:Thrombin inhibits the pertussis-toxin-dependent ADP-ribosylation of a novel soluble Gi-protein in human platelets. 195 57

The vascular tree and the mesangium in the glomerulus respond to various hormones, growth factors, and autonomic signals, leading to generation of second messengers and regulation of ion channels. Guanine nucleotide regulatory proteins (G proteins) mediate these effects in other systems. Glomerular G proteins were studied by immunoblotting and immunohistochemical techniques. Glomeruli were isolated from bovine kidney cortex by differential sieving. Glomerular proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and nitrocellulose transfers were immunoblotted with antibodies to G proteins. G alpha,common antiserum (P-960) recognized proteins with a molecular mass of 41 to 45 kDa. Antibodies against peptide sequences specific to Gi alpha and Go alpha demonstrated Gi alpha, 1/3 (molecular mass, 39 to 41 kDa), Gi alpha 2 (molecular mass, 40 kDa), and Go alpha (molecular mass, 39 kDa). Presence of these proteins was further confirmed by pertussis toxin-catalyzed ADP ribosylation of protein(s) with a molecular mass of 39 to 41 kDa in the glomeruli. Immunohistochemical staining of frozen sections from bovine kidney cortex revealed the presence of Gi alpha 2 in capillary loop distribution in glomeruli and interstitium, but Gi,1/3 or Go could not be demonstrated. The pattern of immunofluorescence with Gi alpha 2 antiserum suggested localization of Gi alpha 2 to the endothelium in glomerular and interstitial vasculature. The novel finding of Go in glomeruli requires localization of Go to specific cells and determination of its role in glomerular physiology. In conclusion, these studies demonstrate that bovine kidney glomeruli express alpha subunits of pertussis toxin-sensitive GTP-binding proteins Gi,1/3, Gi,2 and Go.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification and localization of pertussis toxin-sensitive GTP-binding proteins in bovine kidney glomeruli. 195 30

The abundance of the alpha and beta subunits of the GTP-binding proteins (G-proteins) that transduce hormonal messages to adenylate cyclase was assessed in adipocyte membranes from lean (+/+) and obese (ob/ob) mice, using ADP-ribosylation with bacterial toxin and immunodetection. Both methods revealed two Gs alpha species (48 and 42 kDa) in the membranes. Compared with those of lean mice, the membranes from obese mice contained substantially less of the 48 kDa species of Gs alpha, as assessed by both methods. ADP-ribosylation by pertussis toxin showed that only half as much ADP-ribose was incorporated into Gi alpha in the membranes from obese as compared with lean mice. Immunodetection revealed two separate Gi alpha peptides (39 and 40 kDa) and showed that the 40 kDa species was less abundant in the membranes from obese mice, whereas the amount of the 39 kDa species was similar in membranes from both lean and obese animals. Based on ADP-ribosylation assays, in membranes from lean mice the ratio Gs alpha/Gi alpha was 1:16, whereas in the membranes from obese mice it was 1:10. Similar amounts of immunodetectable beta peptide were found in both types of membranes. On the basis of the currently accepted dissociation model of adenylate cyclase activation, the decrease in the abundance of the Gi alpha subunit in adipocyte membranes from obese mice could account for the abnormal kinetics of the enzyme in these membranes.
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PMID:Quantification of the alpha and beta subunits of the transducing elements (Gs and Gi) of adenylate cyclase in adipocyte membranes from lean and obese (ob/ob) mice. 216 Aug 13

The predominant guanine nucleotide-binding protein (G-protein) of bovine lung membranes, termed GL, has been purified and compared biochemically, immunochemically and functionally with Gi and Go purified from rabbit brain. The purified GL appeared to have a similar subunit structure to Gi and Go, being composed of alpha, beta and possibly gamma subunits. On Coomassie Blue-stained SDS/polyacrylamide gels and immunoblots, the alpha subunit of GL (GL alpha) displayed an intermediate mobility (40 kDa) between those of Gi and Go (Gi alpha and Go alpha). GL alpha was [32P]ADP-ribosylated in the presence of pertussis toxin and [32P]NAD+. Analysis of [32P]ADP-ribosylated alpha subunits by SDS/polyacrylamide-gel electrophoresis and isoelectric focusing showed that GL alpha was distinct from Gi alpha and Go alpha, but very similar to the predominant G-protein in neutrophil membranes. Immunochemical characterization also revealed that GL was distinct from Gi and Go, but was indistinguishable from the G-protein of neutrophils, which has been tentatively identified as Gi2 [Goldsmith, Gierschik, Milligan, Unson, Vinitsky, Maleck & Spiegel (1987) J. Biol. Chem. 262, 14683-14688]. In functional studies, higher Mg2+ concentrations were required for guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[35S]) binding to GL than were required for nucleotide binding to Go, whereas Gi showed a Mg2+-dependence similar to that of GL. The kinetics of GTP[35S] binding to GL was quite different from those of Gi and Go; t1/2 values of maximal binding were 30, 15 and 5 min respectively. In contrast, the rate of hydrolysis of [gamma-32P]GTP by GL (t1/2 approximately 1 min) was approx. 4 times faster than that by Gi or Go. These results indicated that the predominant G-protein purified from lung is structurally and functionally distinct from Gi and Go of brain, but structurally indistinguishable from Gi2 of neutrophils.
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PMID:Purification and characterization of predominant G-protein from bovine lung membranes. Biochemical and immunochemical comparison with Gi1 and Go purified from brain. 249 37

In muscle, it has been established that guanosine 5'-[gamma-thio]triphosphate (GTP[S]), a non-hydrolysable GTP analogue, elicits a rise in tension in chemically skinned fibres, and that pretreatment with Bordetella pertussis toxin (PTX) decreases GTP[S]-induced tension development [Di Virgilio, Salviati, Pozzan & Volpe (1986) EMBO J. 5, 259-262]. In the present study, G-proteins were analysed by PTX-catalysed ADP-ribosylation and by immunoblotting experiments at cellular and subcellular levels. First, the nature of the G-proteins present in neural and aneural zones of rat diaphragm muscle was investigated. PTX, known to catalyse the ADP-ribosylation of the alpha subunit of several G-proteins, was used to detect G-proteins. Three sequential extractions (low-salt-soluble, detergent-soluble and high-salt-soluble) were performed, and PTX was found to label two substrates of 41 and 40 kDa only in the detergent-soluble fraction. The addition of pure beta gamma subunits of G-proteins to the low-salt-soluble extract did not provide a way to detect PTX-catalysed ADP-ribosylation of G-protein alpha subunits in this hydrophilic fraction. In neural as well as in aneural zones, the 39 kDa PTX substrate, very abundant in the nervous system (Go alpha), was not observed. We then studied the nature of the G alpha subunits present in membranes from transverse tubules (T-tubules) purified from rabbit skeletal muscle. Only one 40 kDa PTX substrate was found in T-tubules, known to be the key element of excitation-contraction coupling. The presence of a G-protein in T-tubule membranes was further confirmed by the immunoreactivity detected with an anti-beta-subunit antiserum. A 40 kDa protein was also detected in T-tubule membranes with an antiserum raised against a purified bovine brain Go alpha. The presence of two PTX substrates (41 and 40 kDa) in equal amounts in total muscle extracts, compared with only one (40 kDa) found in purified T-tubule membranes, suggests that this 40 kDa PTX substrate might be involved in excitation-contraction coupling.
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PMID:G-proteins in skeletal muscle. Evidence for a 40 kDa pertussis-toxin substrate in purified transverse tubules. 314 Aug 2

Endothelium-dependent, pertussis toxin-sensitive relaxations are impaired selectively after regeneration of endothelial cells following balloon denudation of the porcine coronary artery. The present study was designed to examine the hypothesis that there is a difference in G proteins modified by pertussis toxin between regenerated and intact endothelial cells. Yorkshire pigs, fed a high-cholesterol diet, underwent balloon denudation of the endothelium of the left anterior descending coronary arteries (LAD). Four weeks after the denudation the animals were killed to detect G proteins by ADP ribosylation catalyzed with pertussis toxin and [32P]NAD, separated on a urea gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In membrane fractions of endothelial cells obtained from previously denuded LAD, G alpha i-1/G alpha i-3 (41 kDa) and G alpha 1-2 (40 kDa) proteins were labeled. The two bands revealed on the gel were the same as those obtained from intact left circumflex coronary arteries (LCX). However, the intensity of the bands was less prominent in the LAD than the LCX. These results suggest that either a decreased amount or a reduced functionality of Gi proteins in the regenerated endothelial cells may account for the impairment in the pertussis toxin-sensitive relaxations after balloon injury of coronary arteries in the pigs.
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PMID:Pertussis toxin-sensitive G proteins in regenerated endothelial cells of porcine coronary artery. 809 1

Heterotrimeric G proteins, consisting of alpha, beta, and gamma subunits, are implicated in major signal transduction pathways controlling a diversity of functions in eukaryotic organisms. In the filamentous fungus Neurospora crassa, G proteins are implicated in the regulation of several environmental responses. As a first step in studying the role of G proteins in these processes, we have cloned the genes for two alpha subunits, gna-1 and gna-2, from Neurospora. The genes are located on different chromosomes and are differentially regulated during asexual development. The encoded proteins (Gna-1 and Gna-2) are the same size as members of the Gi-alpha family (approximately 40 kDa). The Gna-1 protein sequence is 55% identical overall to members of the Gi family and contains the consensus sequences for ADP-ribosylation by pertussis toxin and incorporation of myristic acid, which are found in this group. These properties make Gna-1 the first identified microbial alpha subunit to be a member of any class. Furthermore, incubation of a N. crassa plasma membrane fraction with pertussis toxin results in ADP-ribosylation of a protein substrate which is the approximate size of Gna-1. The predicted Gna-2 protein sequence does not share a high degree of sequence identity with the Gi class. However, the coding region contains at least one intron in a position conserved in the Gi family. We propose that the Gi family of alpha subunits is ancient and during evolution may have first appeared in filamentous fungi.
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PMID:Identification of a G protein alpha subunit from Neurospora crassa that is a member of the Gi family. 832 59

Muscarinic acetylcholine receptor subtypes (m1-m5) differentially regulate phosphoinositide-specific phospholipase (PLC) through the activation of distinct guanine nucleotide-binding (G) proteins which can be distinguished on the basis of their sensitivity to inhibition by pertussis toxin (PTX). In transfected Chinese hamster ovary cells, the m2 receptor subtype regulates the stimulation of PLC and inhibition of adenylyl cyclase (AC) through PTX-sensitive G proteins. In this study, we utilized the ability of cholera toxin (CTX) to ADP-ribosylate PTX-sensitive alpha subunits as part of the ternary complex formed by heterotrimeric G proteins and agonist-bound receptors to detect and characterize the interactions between transfected m2 receptors and endogenous G proteins in Chinese hamster ovary cells. In membranes derived from cells expressing the m2, but not the m3 receptor, the cholinergic agonist carbachol stimulated CTX modification of a 40-kDa species (G alpha 40). Importantly, similar carbachol dose dependence values and PTX dose sensitivities were observed for m2 receptor-mediated PLC signaling and G alpha 40-CTX modification. High resolution urea-SDS-polyacrylamide gel electrophoresis analysis revealed that G alpha i2 (40 kDa) and G alpha i3 (41 kDa) were components of the G alpha 40 identified by m2 receptor-dependent CTX modification. Furthermore, the sensitivities of G alpha i2 and G alpha i3 to PTX modification were determined to be the same as those for PTX inhibition of G alpha 40 labeling by CTX and m2 receptor-mediated PLC signaling. Similarly, agonist-induced desensitization of m2 receptor-G protein signaling required doses of agonist associated with stimulation of PLC. Desensitization involved receptor sequestration and down-regulation of G alpha i3; however, only the reduction of G alpha i3 required prior activation PLC signaling. Finally, desensitization of m2-G protein coupling could be partially mimicked by treatment with thapsigargin, an inducer of intracellular Ca2+ release, without altering the number of cell surface receptors or G protein levels. These results demonstrate that m2 receptors couple to both G alpha i2 and G alpha i3 in vivo and that this interaction is integral to both positive and negative regulatory pathways leading to activation of PLC and desensitization of receptor signaling.
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PMID:Transfected m2 muscarinic acetylcholine receptors couple to G alpha i2 and G alpha i3 in Chinese hamster ovary cells. Activation and desensitization of the phospholipase C signaling pathway. 844 30

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