Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Previously, we have extensively studied FSH-receptor interactions using bovine calf testis membranes, and demonstrated that the high-affinity FSH binding to receptors and coupling of FSH receptors with guanine nucleotide-binding protein (Gs protein) in a GTP-sensitive state are important initial events in FSH action. In this study, using the same plasma membrane system, we examined the glycoprotein nature of the FSH receptor and determined the contribution of carbohydrate moieties to these functions of the FSH receptor. Our approach involved enzymic deglycosylation of FSH receptors present in calf testis plasma membranes and then removal of incompletely deglycosylated FSH receptors by lectin affinity chromatography. Following treatment of testis membranes with peptide N-glycosidase, the receptor, as identified by ligand-blot analysis, had a higher electrophoretic mobility indicating a decrease in M(r) from 240-200K. Treatment of testis membranes with neuraminidase caused a reduction (to approximately 225K) in the size of the receptor consistent with desialylation. However, digestion with O-glycosidase (endo-alpha-N-acetylgalactosaminidase) did not affect the mobility of the FSH receptor. These results suggest that bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains, a finding which is consistent with recent predictions that N-linked glycosylation, but not O-linked glycosylation sites are present in cloned FSH receptor from rat testis. Moreover, calf testis membranes after treatment with peptide N-glycosidase F, were solubilized with Triton X-100 under optimum conditions that preserve the physical and functional coupling of FSH receptors with guanine nucleotide-binding protein, and then subjected to lectin affinity chromatography. Scatchard analysis indicated that intact and deglycosylated FSH receptors bound 125I-human FSH with similar affinities. In the presence of GTP, the binding of 125I-human FSH to intact and deglycosylated receptors decreased similarly and in a noncompetitive manner. Treatment of testis membranes with NAD plus cholera toxin, but not NAD plus pertussis toxin, eliminated the GTP effect on FSH binding to enzymic deglycosylated as well as intact receptors, suggesting that the guanine nucleotide binding protein mediating GTP regulation of FSH binding in these membranes is probably Gs protein. Our results suggest that the bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains consistent with recently predicted N-linked glycosylation sites of cloned FSH receptor of rat testis. The bovine testis FSH receptor does not require N-linked carbohydrate for high-affinity hormone binding.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carbohydrate moiety of follitropin receptor is not required for high affinity hormone-binding or for functional coupling between receptor and guanine nucleotide-binding protein in bovine calf testis membranes. 142 41

The guanine nucleotide-binding protein G(o alpha) has been implicated in the regulation of Ca2+ channels in neural tissues. Covalent modification of G(o alpha) by pertussis toxin-catalyzed ADP-ribosylation of a cysteine (position 351) four amino acids from the carboxyl terminus decouples G(o alpha) from receptor. To define the structural requirements for ADP-ribosylation, preparations of recombinant G(o alpha) with mutations within the five amino acids at the carboxyl terminus were evaluated for their ability to serve as pertussis toxin substrates. As expected, the mutant in which cysteine 351 was replaced by glycine (C351G) was not a toxin substrate. Other inactive mutants were G352D and L353 delta/Y354 delta. Mutations that had no significant effect on toxin-catalyzed ADP-ribosylation included G350D, G350R, Y354 delta, and L353V/Y354 delta. Less active mutants were L353G/Y354 delta, L353A/Y354 delta, and L353G. ADP-ribosylation of the active mutants, like that of wild-type G(o alpha), was enhanced by the beta gamma subunits of bovine transducin. It appears that three of the four terminal amino acids critically influence pertussis toxin-catalyzed ADP-ribosylation of G(o alpha).
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PMID:Pertussis toxin-catalyzed ADP-ribosylation of G(o) alpha with mutations at the carboxyl terminus. 151 Sep 59

Serotonin is a neuromodulator that mediates a wide range of effects by interacting with multiple receptors. Using a strategy based on nucleotide sequence homology between genes encoding receptors that interact with guanine nucleotide-binding proteins, we have isolated a mouse gene encoding an additional serotonin receptor. When expressed in cultured cells, it displayed the pharmacological profile and coupling with adenylate cyclase characteristic of the 5HT1B receptor subtype. In NIH 3T3 cells expressing this receptor, serotonin induced a decrease in forskolin-stimulated cAMP levels. This effect was blocked by pertussis toxin, indicating that the 5HT1B receptor interacts with a pertussis toxin-sensitive guanine nucleotide-binding protein. To obtain clues as to the possible function of the 5HT1B receptor, we have analyzed its pattern of expression in the adult mouse brain by in situ hybridization. Our results, together with previous autoradiographic studies, suggest that the 5HT1B receptors are localized presynaptically on the terminals of striatal neurons and Purkinje cells and that they might modulate the release of neurotransmitters such as gamma-aminobutyric acid. The predominant expression of the 5HT1B receptor in the striatum and cerebellum points to an involvement of this receptor in motor control.
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PMID:Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. 155 7

Exposure to IFN-gamma increases the respiratory burst of polymorphonuclear leukocytes stimulated by the chemoattractant FMLP. However, the mechanism by which IFN-gamma alters the response to FMLP is unclear. We addressed the hypothesis that IFN-gamma enhances the response to FMLP by regulating the expression of elements of the formyl peptide receptor transmembrane-signaling pathway. HL-60 granulocytes were used as a model of FMLP transmembrane signaling. Formyl peptide receptor number and affinity were studied in isolated plasma membranes prepared from control HL-60 cells (CM) and cells exposed to IFN-gamma 100 U/ml for 24 h (IFN-M). Formyl peptide receptors were significantly increased on IFN-M compared with CM (1473 +/- 300 vs 3209 +/- 924). FMLP stimulates increased guanine nucleotide-binding protein (G protein) activation in IFN-M as evidenced by enhanced guanosine 5'-[gamma-thio]triphosphate binding and GTPase activity. Gi sub-unit content was increased in IFN-M as measured by pertussis toxin-catalyzed ADP-ribosylation and immunoblotting with antibodies against alpha i2 and alpha i3 G protein subunits. Guanosine 5'-[gamma-thio]triphosphate equilibrium binding demonstrated an increased number of G proteins coupled to formyl peptide receptors on IFN-M. We conclude that IFN-gamma increases expression of both formyl peptide receptors and G proteins coupled to these receptors, thereby enhancing FMLP-stimulated transmembrane signaling. Regulation of transmembrane signaling element expression may be a significant mechanism by which IFN-gamma regulates cellular functions.
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PMID:IFN-gamma enhances expression of formyl peptide receptors and guanine nucleotide-binding proteins by HL-60 granulocytes. 156 Feb 4

Histamine activation of H1 receptors stimulates 3H release from cultured bovine adrenal chromaffin cells preloaded with [3H]noradrenaline. The initial (1-min) release induced by a high concentration of histamine was unaffected by the removal of extracellular Ca2+, whereas the more sustained response (10 min) was largely inhibited. In contrast, release induced by nicotine was dependent on extracellular Ca2+ at all times. The protein kinase inhibitor staurosporine inhibited both the initial and sustained (10-min) phases of histamine-induced release (IC50 in the region of 200 nM) but was ineffective against a direct depolarizing stimulus (56 mM K+). In contrast, the calmodulin antagonist trifluoperazine was equally effective against both stimuli. These data indicate that although a staurosporine-sensitive event (perhaps involving protein kinase C) is essential for coupling histamine receptor activation to the release processes, it is not essential for exocytosis itself. A further distinction between histamine- and depolarization-induced release was demonstrated by the differential effect of the guanine nucleotide-binding protein inhibitor pertussis toxin. Pretreatment with pertussis toxin (0.1 microgram/ml for 16 h) enhanced depolarization-induced release by approximately 1.5-fold. This pertussis toxin pretreatment was, however, approximately twofold as effective in potentiating histamine-evoked release. Thus, the characteristics of the histaminergic response are distinct from those of a depolarizing stimulus, perhaps indicating the involvement of different mechanisms in the release process.
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PMID:Characterization of histamine-induced catecholamine secretion from bovine adrenal medullary chromaffin cells. 156 Feb 21

A growing body of evidence suggests that tricyclic antidepressant agents (TCAs) interact with GTP binding proteins (G proteins). We have investigated if TCAs directly alter the function of the purified Go protein which is specifically expressed in neuronal tissue. Several TCAs markedly enhanced the GTPase activity of Go protein in a pertussis toxin-susceptible manner, whereas MAO-inhibitor and anxiolytic agent did not. This enhancing effect of TCAs on Go function may be due to an increase in the GDP-GTP exchange reaction occurring on Go. Thus, it is very likely that TCAs can modify various signal transduction by directly interacting with G proteins in brain cells.
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PMID:Direct activation of purified Go-type GTP binding protein by tricyclic antidepressants. 160 49

Cerebral ischemia produces perturbation of signal transduction systems in neurons. In order to estimate the contribution of guanine nucleotide-binding protein (G-protein) to hippocampal neuronal death, the effect of pertussis toxin (PTX) on the CA1 pyramidal cell damage after transient forebrain ischemia in rats was examined. PTX was administered 3 days before 20 min of transient forebrain ischemia. PTX injection into the CA1 subfield failed to alter the number of ischemic-damaged CA1 pyramidal cells. In contrast, ventricular PTX injection exacerbated CA1 pyramidal cell damage. We also studied postischemic alteration of GTP binding sites in the hippocampal formation using quantitative in vitro autoradiography. Autoradiographic imaging demonstrated predominant distribution of GTP binding sites in synaptic areas in the hippocampus. No significant change of GTP binding activity was observed in the hippocampus until 2 days after recirculation. Seven days after ischemia, when the CA1 pyramidal cells were depleted, the GTP binding sites of the strata oriens and radiatum in the CA1 subfield had reduced by 32% and 31%, respectively. In contrast, GTP binding in the CA3 subfield and the dentate gyrus remained unaltered throughout the reperfusion period. These results suggest that the amount of G-proteins as estimated by GTP binding remained unaltered in the hippocampus during the early recirculation period, when the CA1 pyramidal cells were morphologically intact, and that signal transduction pathways mediated by Gi and Go do not play a major role in delayed death of the CA1 pyramidal cells.
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PMID:The role of GTP binding proteins in ischemic brain damage: autoradiographic and histopathological study. 161 6

In response to a meiosis-inducing hormone, 1-methyladenine (1-MA), starfish oocytes undergo reinitiation of meiosis with germinal vesicle breakdown. The 1-MA-initiated signal is, however, inhibited by prior microinjection of pertussis toxin into the oocytes, suggesting that a guanine nucleotide-binding protein (G protein) serving as the substrate of pertussis toxin is involved in the 1-MA receptor-mediated signal. We thus investigated properties of 1-MA receptors by means of binding of the radiolabeled ligand to the oocyte membranes. There were apparently two forms of 1-MA receptors with high and low affinities in the membranes. The high-affinity form was converted into the low-affinity one in the presence of a non-hydrolyzable analogue of GTP. A 39-kDa protein, which had been identified as the alpha-subunit of the major substrate G protein for pertussis toxin, was also ADP-ribosylated by cholera toxin only when 1-MA was added to the membranes. The ADP-ribosylated 39-kDa alpha-subunit could be immunoprecipitated with antibodies raised against the carboxy-terminal site of mammalian inhibitory G-alpha. These results indicate that 1-MA receptors are functionally coupled with the 39-kDa pertussis toxin-substrate G protein in starfish oocyte membranes.
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PMID:Properties of 1-methyladenine receptors in starfish oocyte membranes: involvement of pertussis toxin-sensitive GTP-binding protein in the receptor-mediated signal transduction. 163 62

Treatment of cultured rat cardiomyocytes in serum-free medium for 48 h with recombinant human tumor necrosis factor alpha (TNF alpha) led to a concentration-dependent increase in the level of membrane-inhibitory guanine nucleotide-binding protein (Gi) alpha-subunits and in pertussis toxin-catalyzed [32P]ADP ribosylation of 40 kDa proteins. Both Gi alpha protein subtypes present in rat cardiac myocyte membranes, Gi alpha 40 and Gi alpha 41, were up-regulated by the cytokine, with the maximal increase occurring at 10 U/ml TNF alpha. In contrast to noradrenaline exposure, which causes a similar, but apparently exclusive, increase in alpha i-subunits, treatment with TNF alpha in addition increased the level of membrane G protein beta 36-subunits. Furthermore, while noradrenaline exposure led to a decrease in receptor-dependent and -independent adenylyl cyclase activity, treatment of cardiomyocytes with TNF alpha caused a concentration-dependent increase in cyclase responsiveness to either forskolin, guanosine 5'-O-(3-thiotriphosphate) or isoproterenol, even though beta-adrenoceptor density was decreased by TNF alpha. The increase in adenylyl cyclase activity induced by TNF alpha was completely suppressed when the cells were cocultured with noradrenaline, a condition leading to an additive increase in Gi alpha level. The data indicate that the cytokine TNF alpha can potently modulate G protein-mediated signal transduction in rat cardiac myocytes. Although TNF alpha, like noradrenaline, exposure of the cells increased the level of membrane Gi alpha proteins, it did not decrease but rather caused an increase in adenylyl cyclase responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor alpha up-regulates Gi alpha and G beta proteins and adenylyl cyclase responsiveness in rat cardiomyocytes. 164 97

We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to encode a heretofore undetermined member of the guanine nucleotide-binding protein (G protein)-linked receptor family. The human clone we isolated, called MA6A, contains an apparently intronless open reading frame encoding a 377-amino acid polypeptide with the seven hydrophobic domains characteristic of G protein-linked receptors. The MA6A deduced amino acid sequence is 88% identical to that for RDC4 and 43% identical to that for the human 5-HT1A receptor. Expression of the human gene product in transfected cell lines results in the appearance of saturable high affinity 5-HT1D-type [3H]5-HT binding. The expressed receptor exhibits features indicative of coupling to Gi proteins, i.e., robust inhibition of forskolin-stimulated cAMP accumulation and formation of a pertussis toxin-sensitive high agonist affinity binding state. These findings may help clarify several ambiguities in the classification and action of serotonin receptor subtypes.
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PMID:Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. 165 50


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