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)

The cDNAs encoding the murine LH receptor (LHR) and the human beta 2-adrenoceptor (h beta 2AR) were cloned and RNAs complementary to their sense strands (cRNAs) were injected into defolliculated Xenopus oocytes. This led to expression, respectively, of LH- and isoproterenol-stimulable adenylyl cyclase activities, indicating that functionally active receptor cDNAs had been cloned. In oocytes injected with LHR cRNA, but not in control or h beta 2AR cRNA-injected oocytes, human CG and LH increased a Ca(2+)-activated Cl- current, as measured by the two-microelectrode voltage-clamp method. This effect was not seen with isoproterenol in control or h beta 2AR cRNA-injected oocytes, it was also not observed in response to forskolin or (Bu)2cAMP. The response to human CG could be obtained in the absence of extracellular Ca2+ but was abolished by injection of EGTA, indicating that it was caused by mobilization of Ca2+ from intracellular stores. The response was unaffected by overnight treatment with 1 microgram/ml pertussis toxin. The experiments show that a glycoprotein hormone receptor can be expressed as a functionally active molecule in Xenopus oocytes, and that the LHR has the ability of activating two separate intracellular signaling pathways: one forming the second messenger cAMP, and the other mobilizing Ca2+ from intracellular stores. It is proposed that the latter is secondary to a primary activation of phospholipase C by the LHR, which elevates intracellular Ca2+ via intermediary elevation of inositol phosphates, presumably (1,4,5)inositol trisphosphate.
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PMID:Ca2+ mobilization by the LH receptor expressed in Xenopus oocytes independent of 3',5'-cyclic adenosine monophosphate formation: evidence for parallel activation of two signaling pathways. 131 58

A somatostatin (SRIF) receptor and its associated Gi regulatory proteins was purified from GH4C1 rat pituitary cells by: 1) saturation of the membrane-bound receptor with biotinyl-NH-[Leu8,D-Trp22,Tyr25] SRIF28 (bio-S28); 2) solubilization of receptor-ligand (R.L) complex with deoxycholate-lysophosphatidylcholine (D.L); 3) adsorption of solubilized receptor-ligand complex to immobilized streptavidin; and 4) elution of receptor and G-protein by GTP. The receptor, a glycoprotein with an average M(r) of 85,000, was then purified to substantial homogeneity on immobilized wheat germ agglutinin. The 85-kDa glycoprotein was identified as a SRIF receptor by several criteria. (a) It had the same size as the chemically cross-linked R.[125I]L complex. (b) Yield of the purified protein increased and plateaued in the same range of bio-S28 concentrations where specific high affinity binding reached saturation. (c) It was copurified with appropriate G-protein subunits. The 85-kDa receptor and two other proteins with M(r) values of 35,000 and 40,000, the sizes of G beta and G alpha, did not appear in eluates from control streptavidin columns done with SRIF receptors loaded with nonbiotinylated S14. The 40-kDa protein was identified as a Gi alpha by ADP-ribosylation from [32P]NAD catalyzed by pertussis toxin. (d) Both the chemically cross-linked R.[125I]L complex and SRIF receptor purified from [35S]methionine-labeled GH4C1 cells were reduced in size to about 38 kDa by endoglycosidase F. (e) Amino acid sequence from the purified receptor was nearly identical with that of a recently cloned SRIF receptor subtype.
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PMID:Purification of a pituitary receptor for somatostatin. The utility of biotinylated somatostatin analogs. 135 97

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

Zona pellucida (ZP)-induced acrosomal exocytosis in mammalian spermatozoa is thought to be mediated by signal transduction cascades similar to those found in hormonally responsive cells. In order to characterize this process further, we have examined the role of GTP-binding regulatory proteins (G proteins) in coupling sperm-ZP interaction to intracellular second messenger systems in mouse sperm. An in vitro signal transduction assay was developed to assess ZP-G protein dynamics in sperm membrane preparations. Guanosine 5'-3-O-(thio)triphosphate (GTP gamma S), a poorly hydrolyzable analogue of GTP, bound to these membranes in a specific and concentration-dependent fashion which reached saturation at 100 nM. Incubation of the membrane preparations with heat-solubilized ZP resulted in a significant increase in specific GTP gamma S binding in a concentration-dependent fashion with a half-maximal response at 1.25-2 ZP/microliters. Solubilized ZP also caused a significant increase in high affinity GTPase activity in the membranes over basal levels. Mastoparan increased specific GTP gamma S binding to the sperm membranes and stimulated high-affinity membrane GTPase activity to levels consistently greater than that seen with the solubilized ZP. Mastoparan, together with solubilized ZP, gave the same level of stimulation of GTP gamma S binding as mastoparan alone. Pertussis toxin completely inhibited the ZP-stimulated GTP gamma S binding, but only decreased mastoparan-stimulated GTP gamma S binding by 70-80%. Purified ZP3, the ZP component which possesses quantitatively all of the acrosomal exocytosis-inducing activity of the intact ZP, stimulated GTP gamma S binding to the same level as solubilized ZP; ZP1 and ZP2 did not stimulate GTP gamma S binding. ZP from fertilized eggs (ZPf), which does not possess acrosome reaction-inducing activity, also failed to stimulate GTP gamma S binding to sperm membranes. These data demonstrate the direct activation of a Gi protein in sperm membrane preparations in response to the ZP glycoprotein, ZP3, that induces the acrosome reaction. These data imply that Gi protein activation is an early event in the signal sequence leading to sperm acrosomal exocytosis.
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PMID:Activation of a Gi protein in mouse sperm membranes by solubilized proteins of the zona pellucida, the egg's extracellular matrix. 162 5

Histamine stimulation of gastric acid secretion has for a long time been known to be mediated by an H2-type receptor located on the parietal cell surface, but the biochemical nature of this receptor has only very recently been elucidated. It is a 70-kDa glycoprotein showing structural analogies with the beta 2-adrenergic receptor and the other seven membrane-spanning domains/G protein-coupled receptors. It activates adenylated cyclase through a cholera toxin-sensitive, pertussis toxin-insensitive, guanosine 5'-triphosphatase-binding regulatory Gs protein. The cAMP thereby produced is believed to play a crucial role in the opening of the Cl- channel associated with the (H+,K+)-ATPase in the secretory membrane. However, other sites of action are likely to be involved, since several histamine- or cAMP-dependent phosphoproteins have been detected in the parietal cell. In addition to its action on cAMP production, histamine was found to produce a transient increase in the intracellular Ca2+ concentration, but this effect remains unexplained. On the other hand, the intervention of an H3-type histamine receptor in the regulation of gastric acid secretion has recently been documented, but the cellular location of this new receptor has not been yet investigated.
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PMID:Receptors regulating acid secretion. 164 88

Receptor tyrosine kinases couple to multiple intracellular effector molecules that are crucial for normal cell growth and transformation. Stimulation of membrane phospholipid hydrolysis by receptor tyrosine kinases is one such pathway for generating intracellular second messengers that may be important for mitogenesis. Certain receptor tyrosine kinases tyrosine phosphorylate a phosphoinositide-specific phospholipase C that hydrolyses the membrane phospholipid phosphatidylinositol 4,5-bisphosphate. In contrast, the glycoprotein receptor for colony stimulating factor 1, a transmembrane tyrosine kinase, does not utilize this pathway, but rather stimulates the hydrolysis of phosphatidylcholine. Here we show that eluates of antiphosphotyrosine affinity purified lysates of colony-stimulating factor 1-stimulated cells contain elevated levels of phosphatidylcholine-specific phospholipase C activity. The affinity-purified activity is sensitive to tyrosine-specific T-cell phosphatase, and is detected in the membrane fraction of stimulated cells. Recovery of phospholipase C activity in the antiphosphotyrosine protein fraction is reduced by pertussis toxin pretreatment of cells. The phosphatidylcholine phospholipase C activity in isolated membranes of colony-stimulating factor 1-treated cells was also reduced by pertussis toxin treatment and stimulated by guanosine 5'-3-O-(thio)triphosphate. These results indicate that colony stimulating factor 1 receptor-mediated stimulation of phosphatidylcholine-specific phospholipase C requires tyrosine phosphorylation, and might be affected by a G-protein coupled pathway.
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PMID:Activation of a phosphatidylcholine-specific phospholipase C by colony stimulating factor 1 receptor requires tyrosine phosphorylation and a guanine nucleotide-binding protein. 147 33

Activation of the formyl peptide chemoattractant receptor (FPCR) of phagocytic cells mobilizes intracellular calcium stores and affects the plasma membrane potential. Affinity crosslinking of FPCR has demonstrated a 60-80 kDa glycoprotein, with core peptide of 32 kDa. It is not known whether functional FPCR is this single peptide or requires multiple subunits. We used Xenopus oocyte expression system to determine the size of mRNA required for synthesis of functional FPCR. Injection of oocytes with poly(A)+ RNA from HL60 cells differentiated to the granulocyte phenotype resulted in acquisition of formyl peptide-specific responses (inward transmembrane current with a reversal potential consistent with a chloride conductance, and calcium efflux). FPCR activity expressed in oocytes had a ligand concentration dependence, ligand structure dependence and pertussis toxin sensitivity similar to those reported in phagocytic cells. When RNA was size fractionated, a single peak of FPCR activity at 2 kilobases was observed after injection of mRNA into oocytes. Our data strongly suggest that FPCR is composed of a single-sized polypeptide.
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PMID:The formyl peptide chemoattractant receptor is encoded by a 2 kilobase messenger RNA. Expression in Xenopus oocytes. 169 Jan 50

The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of [3H]ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP greater than ATP greater than GTP greater than CTP greater than TTP for pertussis toxin and ATP greater than GTP greater than TTP greater than CTP for the B oligomer. Phosphate ions inhibited the binding of [3H]ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of [3H]ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.
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PMID:Binding of ATP by pertussis toxin and isolated toxin subunits. 169 50

3H-Labelled kappa-elastin peptides (kE:75 kDa molecular weight) were shown to bind to confluent human skin fibroblast (HSF) cultures in a time-dependent and saturable manner. Scatchard analysis indicated the presence of high affinity binding sites with kD = 2.7 x 10(-10) M and 19,000 sites per cell. Binding of kE to its receptor on HSF accelerates and intensifies the adhesion of insoluble elastin fibres (iE) to confluent HSF. Optimal effect was attained for a kE concentration of 0.3 x 10(-9) M close to kD. This stimulatory effect of kE on the binding of iE to HSF could be inhibited by neomycin, retinal and pertussis toxin, substances which act at different levels of the transduction mechanism following the activation of the receptor and the subsequent triggering of cell biological events (chemotaxis, modification of calcium fluxes). The stimulation of iE adhesion to HSF induced by kE as well as kE binding to the cells could be inhibited by lactose and laminin but not by Arg-Gly-Asp-Ser(RGDS) peptides. This indicates that the elastin peptide receptor on HSF possesses lectin-like properties and shares homology with the laminin receptor as also shown for other cell types. None of the substances tested, that is inhibitors of the transduction mechanism, lactose, laminin and Arg-Gly-Asp-Ser(RGDS) peptides were shown to interfere significantly with the binding of iE (in the absence of added kE) to confluent HSF. The proteins adhering strongly to elastin fibres were isolated by a sequential extraction procedure and the final hydrochloride guanidinium-DTT extract was analysed by SDS-PAGE under reducing conditions, Western blots using specific antibodies against several connective tissue proteins and affinity for [3H]-kE following nitrocellulose electro-transfer of proteins. Fibronectin, vitronectin, tropoelastin(s), and a 120 kDa cysteine rich glycoprotein previously designated as elastonectin were identified. Among these proteins, [3H]-kE was found to bind exclusively to a 65 kDa protein that could be eluted selectively from elastin fibres with a neutral buffer containing 100 mM lactose. Therefore the elastin peptide receptor on human skin fibroblasts shares properties with the elastin receptor characterized from other cell types. Conformational differences between elastin peptides and elastin fibres could explain the differences in the mechanisms of interactions between elastin fibres and elastin peptides with HSF in culture. The stimulatory effect of elastin-derived peptides on the adhesion of elastin fibres to HSF could have implications in the oriented biosynthesis of elastin fibres.
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PMID:Mechanisms of interaction between human skin fibroblasts and elastin: differences between elastin fibres and derived peptides. 172 59

The T cell receptor (TcR) heterodimer of alpha/beta glycoprotein is noncovalently associated with CD3 glycoprotein forming TcR/CD3 complex. The TcR have been shown to recognize antigen, and CD3 antigen is responsible for signal transduction. In this study we compared the effects of WT31 (defining alpha/beta TcR) monoclonal antibody (MoAb) and anti-CD3 MoAb on various steps of human T cell activation. Both antibodies depolarized plasma membranes, increased cell volume, induced IL-2 production and the expression of IL-2 receptors (CD25 antigen) and induced DNA synthesis. Furthermore, the two antibodies showed no synergistic effect on any of these parameters. However, both MoAb showed synergism with phorbol ester (PMA). WT31-induced T cell activation was Ca(2+)-dependent because the addition of EGTA to the medium inhibited DNA synthesis and CD25 antigen expression. The blockers of protein kinase C (PKC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and staurosporin, in a dose-dependent manner inhibited WT31-induced DNA synthesis. Cholera toxin but not the pertussis toxin inhibited WT31-induced T cell activation, suggesting involvement of G protein in WT31-induced T cell activation. These data indicate that WT31 antibody activates human T cells by a pathway that is similar to that of anti-CD3-induced T cell activation.
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PMID:T cell activation via the T cell receptor: a comparison between WT31 (defining alpha/beta TcR)-induced and anti-CD3-induced activation of human T lymphocytes. 182 55

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