Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CC chemokines regulated on activation normal T expressed and secreted (RANTES) and monocyte chemotactic protein 3 (MCP-3), and the anaphylatoxin C5a, induce activation, degranulation, chemotaxis, and transendothelial migration of eosinophils. Adhesion assays on purified ligands showed differential regulation of beta 1 and beta 2 integrin avidity in eosinophils. Adhesiveness of VLA-4 (alpha 4 beta 1, CD29/CD49d) for vascular cell adhesion molecule 1 or fibronectin was rapidly increased but subsequently reduced by RANTES, MCP-3, or C5a. The deactivation of VLA-4 lead to cell detachment, whereas phorbol 12-myristate 13-acetate induced sustained activation of VLA-4. In contrast, chemoattractants stimulated a prolonged increase in the adhesiveness of Mac-1 (alpha M beta 2, CD11b/CD18) for intercellular adhesion molecule 1. Inhibition by pertussis toxin confirmed signaling via G protein-coupled receptors. Chemoattractants induced transient, while phorbol 12-myristate 13-acetate induced sustained actin polymerization. Disruption of actin filaments by cytochalasins inhibited increases in avidity of VLA-4 but not of Mac-1. Chemoattractants did not upregulate a Mn2+-inducible beta 1 neoepitope defined by the mAb 9EG7, but induced prolonged expression of a Mac-1 activation epitope recognized by the mAb CBRM1/5. This mAb inhibited chemoattractant-stimulated adhesion of eosinophils to intercellular adhesion molecule 1. Thus, regulation of VLA-4 was dependent on the actin cytoskeleton, whereas conformational changes appeared to be crucial for activation of Mac-1. To our knowledge, this is the first demonstration that physiological agonists, such as chemoattractants, can differentially regulate the avidity of a beta 1 and a beta 2 integrin expressed on the same leukocyte.
 ...
PMID:Differential regulation of beta 1 and beta 2 integrin avidity by chemoattractants in eosinophils. 885 87

Metabotropic glutamate receptors are G protein-coupled receptors that perform a variety of modulatory roles in the central and peripheral nervous systems. The development of receptor subtype-specific agonists/antagonists has lagged far behind the isolation and characterization of receptor cDNAs. Further more, the coupling of specific metabotropic receptors to the various neuronal-specific effector molecules, such as voltage gated Ca2+ channels, has not been well studied. It was recently demonstrated that a rat group II metabotropic receptor (rm-GluR2) is capable of coupling to endogenous N-type Ca2+ channels when heterologously expressed in adult rat sympathetic ganglia neurons. To eventually understand the molecular aspects of metabotropic receptor modulation of the N-type Ca2+ channel, we have transiently expressed both group II receptors in a human embryonic kidney 293 cell line (G1A1) that stably expresses the human alpha 1B-1, alpha 2b, and beta 1-3 Ca2+ channel subunits. rmGluR2 and rmGluR3 modulate the omega-conotoxin GVIA-sensitive Ba2+ currents in G1A1 cells using a voltage-dependent mechanism via an endogenous pertussis toxin-sensitive G protein. Cell-attached "macropatch" recordings demonstrate that modulation by rmGluR2 and rmGluR3 is membrane delimited. This is the first report of Ca2+ channel modulation mediated by rmGluR3. In addition, an extensive pharmacological comparison between rmGluR2 and rmGluR3 reveals that these group II receptors interact with agonists and antagonists in unique ways.
 ...
PMID:Functional coupling of rat group II metabotropic glutamate receptors to an omega-conotoxin GVIA-sensitive calcium channel in human embryonic kidney 293 cells. 886 37

Aconitine and higenamine are the major cardioactive compounds obtained from processed aconite. The chronotropic interaction between these two compounds was investigated in isolated right atria of mice. Both aconitine and higenamine potentiated the action of the other. Practolol (1 nM), a selective beta 1-adrenergic antagonist, but not butoxamine (1 microM), a beta 2-adrenergic antagonist, blocked the potentiation by higenamine (5 nM) of the aconitine-induced positive chronotropic effect and, at high concentrations (30 and 300 nM) also shifted the aconitine concentration-response curves to the right. The potentiating interaction between aconitine and higenamine was reversed by pretreating with cholera toxin (CTX) and forskolin. In CTX (100 nM, 1 h)- and forskolin (30 and 100 nM)-treated atria, higenamine significantly depressed the aconitine-induced response, which was abolished by pertussis toxin (PTX, 150 micrograms/kg, i.p., 3 d). Neither CTX (50 and 100 nM) nor forskolin (15-100 nM) significantly affected the aconitine-induced positive chronotropic effect, while PTX (150 micrograms/kg) depressed it. These results suggest that the potentiating interaction between aconitine and higenamine involves "cross-talk" between the beta 1-adrenergic signalling pathway and Gi-protein.
 ...
PMID:Potentiation by higenamine of the aconitine-induced positive chronotropic effect in isolated right atria of mice: the effects of cholera toxin, forskolin and pertussis toxin. 887 10

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.
 ...
PMID:Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated. 888 89

The effects of denopamine, a nonparenteral partial beta agonist which is used clinically in Japan, on the L-type Ca2+ current (ICa) were examined in rabbit ventricular cells. Denopamine stimulated basal ICa with a maximum response of +33.2% and a concentration for half-maximal response (EC50) of 0.039 microM. The maximum response of ICa was only a quarter of that induced by isoprenaline (ISO), while 10 microM denopamine elicited 70-75% of the maximum inotropic response in the papillary muscle preparations. The denopamine stimulation of ICa was abolished by selective beta 1 antagonists (atenolol or bisoprolol). Pretreatment with forskolin or dialysis with cAMP also abolished the stimulation. Denopamine, in turn, inhibited ISO-stimulated ICa. This inhibition was not affected by pretreatment with pertussis toxin or prazosin. The presence of denopamine at various concentrations caused a rightward shift in the concentration/response curve for ISO stimulation of ICa. The Schild plot for this effect had a slope of 0.99 and Kp of 0.20 microM. In the presence of guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) (0.5 mM) in the pipette, denopamine (10 microM) stimulated the ICa to 86 +/- 5% of the maximum response induced by ISO. These findings indicate that denopamine modulates ICa exclusively through the beta 1 adrenoceptor-adenylate cyclase pathway, that the stimulatory GTP-binding protein regulates the agonistic potency of denopamine, and that the signal from the beta 1 adrenoceptors is amplified between ICa and the tension development, which would contribute to the spare capacity of beta adrenoceptors.
 ...
PMID:Modulation of L-type Ca current by denopamine, a nonparenteral partial beta 1 stimulant, in rabbit ventricular cells. 889 46

The nature of the autoimmune T cell response to myelin oligodendrocyte glycoprotein (MOG), recently recognized as a potential target antigen in multiple sclerosis (MS), has not yet been characterized, in contrast to the T cell reactivity to other potential target antigens in MS such as myelin basic protein and proteolipid protein. Here, we show that the encephalitogenicity of the recombinant Ig-like domain of human MOG is associated, in H-2 b mice, with an immunodominant T cell reactivity against a single region of MOG spanning amino acids 35-55, accounting for the previously reported strong encephalitogenic activity of pMOG 35-55. A single injection of pMOG 35-55 with or without administration of pertussis toxin was sufficient to induce severe clinical experimental autoimmune encephalomyelitis (EAE) in H-2 b mice. Encephalitogenic pMOG 35-55-specific T cell lines derived from C3H.SW (V beta b) mice were diverse in their TCR V beta gene usage (V beta 1, V beta 6, V beta 8 and V beta 15), although V beta 8.2 was most predominantly expressed (48%). However, V beta 8 + T cells may only be part of the encephalitogenic MOG-specific T cell repertoire in H-2 b mice, as demonstrated by the susceptibility of C57L (V beta a) mice to disease induced by pMOG 35-55. Encephalitogenic T cell lines from V beta a mice were also diverse in their TCR V beta gene usage (V beta 1, V beta 2, V beta 6, V beta 14 and V beta 16). Such a heterogeneous TCT V beta gene expression by pMOG 35-55/I-A b-reactive T cells from both V beta a and V beta b H-2 b mice suggested multiple epitopes within pMOG 35-55. Analysis of the pattern of reactivity by pMOG 35-55-reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40-48). However, optimal stimulation was obtained with longer peptides, with each additional amino acid flanking either the N or the C terminus differentially increasing the stimulatory capacity of pMOG 40-48. Nonetheless, pMOG 40-48 was the minimal encephalitogenic epitope for both V beta a and V beta b mice. Thus, the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse V beta gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope-directed, rather than TCR-targeted, approaches to immunospecific therapy for MOG-related autoimmune disease.
 ...
PMID:Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse V beta gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor V beta b and T cell receptor V beta a H-2b mice. 889 62

Mouse monoclonal antibodies MAHI 4 and MAHI 10 reactive with Haemophilus influenzae lipopolysaccharide (LPS), were generated by fusing mouse myeloma cells with spleen cells of mice immunized with H. influenzae strain RM.7004-XP-1. The antibody MAHI 4 reacted in whole-cell enzyme immunoassay (EIA) and colony-dot-immunoblotting with 20 of 123 H. influenzae strains and to a few other human Haemophilus spp. and Neisseria spp., but not to any Bordetella pertussis, B. parapertussis, Aeromonas spp. or Moraxella catarrhalis strains tested. This suggests a specific epitope accessible to recognition in just a few strains. This conclusion was supported by the data on binding of MAHI 4 to only three of 18 H. influenzae LPSs tested, but not to any Haemophilus ducreyi or enterobacterial LPSs. The antibody MAHI 10 bound to 80 of 123 strains of H. influenzae and to a few strains of Neisseria spp. and M. catarrhalis as evaluated by EIA and colony-dot-immunoblotting, which suggests an epitope accessible to recognition in 65% of the H. influenzae strains tested. The antibody MAHI 10 reacted with 10 of 18 H. influenzae LPSs as determined by EIA. By using polysaccharides, obtained after both mild acidic hydrolysis, strong alkali treatment, and dephosphorylation, as inhibitors of the antibodies binding to H. influenzae LPS antigens it was shown that phosphate groups were essential for the binding of MAHI 10 to LPS but they did not affect antigenic recognition by MAHI 4. None of the monoclonal antibodies bound to isolated lipid A, but the aggregation caused by the fatty acids of lipid A was essential for optimum epitope recognition. Enzymatic treatment of homologous LPSs with galactose-oxidase led to products which were between 20 to 30 times less effective as inhibitors of the binding of the MAHI 4 than the native LPSs. Taken together the results indicate that MAHI 4 has the following pentasaccharide as the epitope Gal beta 1-->2 Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1--> Kdo(P). These results emphasize the importance of the terminal beta-Gal residue in the definition of the MAHI 4 specificity, and of the terminal phosphorylated saccharide residues of some of the Haemophilus LPSs for the MAHI 10 specificity.
 ...
PMID:Monoclonal antibodies against Haemophilus influenzae lipopolysaccharides: clone MAHI 4 binding to a pentasaccharide containing terminal beta-Gal residues and clone MAHI 10 recognizing terminal phosphorylated saccharide residues. 893 39

In plasma membranes derived from bovine mesenteric lymphatic smooth muscle cells, guanine nucleotide and forskolin stimulated adenylyl cyclase (AC) activity in a concentration-dependent manner, indicative of the presence of the stimulatory G-protein Gs linked to AC. There was no significant enzyme inhibition by low concentrations of guanine nucleotide and no effect on basal or guanine nucleotide-stimulated activity following pertussis toxin treatment of cells, suggesting the absence of Gi linked to inhibition of AC. Furthermore, there was no effect of adrenaline, isoprenaline or clonidine on basal or forskolin-stimulated activities, nor was there any specific binding of the beta-adrenoceptor ligand [125I]cyanopindolol to membranes, suggesting that catecholamine receptors do not modulate AC activity in these membranes. Pertussis toxin-mediated ADP ribosylation of membrane proteins and Western immunoblotting analysis revealed the presence of G-protein subunits G alpha i2, G alpha q, and G beta 1. In experiments designed to identify a possible effector enzyme for these G-proteins, membranes were screened with a range of antibodies raised against phospholipase C (PLC) beta, gamma and delta isozymes. Though no evidence was obtained by Western blotting for any of these proteins, PLC activity was concentration-dependently stimulated by Ca2+, but not by AIF4-, GTP[S], or purified G beta gamma subunits. Finally, no specific binding to membranes of the alpha 1-adrenoceptor ligand [3H]prazosin or the alpha 2-adrenoceptor ligand [3H]yohimbine was obtained. In conclusion, this study provides evidence for a Gs-dependent stimulation of AC, and for the presence of Gi2 and Gq/11, which do not appear to regulate a PLC activity also identified in lymphatic smooth muscle cell membranes. Furthermore, neither AC nor PLC appear to be associated with catecholamine receptors.
 ...
PMID:Evidence for the presence of G-proteins, adenylyl cyclase and phospholipase C activities in lymphatic smooth muscle cell membranes. 895 44

Although a physiological role for oxytocin during parturition is well accepted, the mechanisms by which it activates myometrial contractility during labor have not been completely elucidated. We have previously shown the presence of Gq and two pertussis toxin (PT) substrates of the Gi family in human myometrial cells. In the present study, we have identified by Western blotting the G protein and phospholipase C (PLC) isoforms present in these cells and investigated their implication in oxytocin signaling by measuring the formation of inositol phosphates (IPs) and mobilization of intracellular calcium. We found G protein subunits alpha(q), alpha(11), alpha(i1), alpha(i2), alpha(i3), alpha(z), and two splice variants of alpha(s)- and beta-subunits. We have also detected the presence of five PLC isoforms: beta 1, beta 2, beta 3, gamma 1, and gamma 2. Oxytocin-induced IPs formation and intracellular Ca2+ mobilization were inhibited to approximately 50% after pretreatment of the cells with PT, suggesting that oxytocin activates PLC beta by interacting with at least two types of G proteins: a member of the Gq family (PT resistant) and a member of the Gi family (PT sensitive). The tyrosine phosphatase inhibitor pervanadate stimulated IPs formation in myometrial cells. Using the protein kinase inhibitors staurosporine, phenylarsine oxide, and Ro 31-8220 and the protein kinase C activator phorbol dibutyrate, we have shown that pervanadate and oxytocin activate PLC by different mechanisms. Furthermore, oxytocin did not activate tyrosine phosphorylation in human myometrial cells, as measured with an antiphosphotyrosine antibody, indicating that it does not activate a PLC gamma isoform. We conclude that oxytocin activates human myometrium by interacting with at least two G proteins and possibly three PLC beta isoforms.
 ...
PMID:Multiple G proteins and phospholipase C isoforms in human myometrial cells: implication for oxytocin action. 896 34

Heterotrimeric G-proteins have been found in eukaryotic cells, from yeast to humans, but have received little attention, to date, with respect to parasitic organisms. We now present the first report of the characterization of heterotrimeric G-proteins expressed in a filarial nematode, Acanthocheilonema viteae. Using a combination of (i) affinity labelling with [alpha-32P]GTP; (ii) ADP-ribosylation with cholera toxin and pertussis toxin; (iii) Western blotting with a panel of anti-G-protein antibodies; and (iv) reverse transcriptase-PCR with degenerate G-protein oligonucleotide primers followed by hybridization analysis using oligonucleotides specific for individual G-protein subunits, we demonstrate that adult A. viteae expresses homologues of the beta 1- and/or beta 2-like subunits and alpha-subunits of the Gs, G1, Gq and G12 subfamilies found in mammals. The role which these G-proteins may play in the biology of the organism is discussed.
 ...
PMID:Characterization of heterotrimeric G-proteins in adult Acanthocheilonema viteae. 897 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>