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)

Mechanical loading plays an important role in regulating bone remodeling, and nitric oxide may be one regulator of this process. To determine how mechanical stress modulates osteoblast function, we loaded cyclic tensile stretch on osteoblast-like cells and measured levels of nitric oxide in the medium. High frequency of stretch at any magnitude inhibited release of nitric oxide; however, low frequency of stretch enhanced its release from the static control. To examine the involvement of G protein (guanine nucleotide-binding regulatory protein) in stress-inhibited release of nitric oxide, we added pertussis toxin, a specific inhibitor of the Gi class, and found that it completely reversed the stress-inhibited release. These data support the idea that pertussis toxin-sensitive G protein is activated in the presence of cyclic tensile stretch.
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PMID:Pertussis toxin-sensitive G proteins as mediators of stretch-induced decrease in nitric-oxide release of osteoblast-like cells. 1045 68

Mel 1a melatonin receptors belong to the super-family of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors. So far, interest in Mel 1a receptor signaling has focused mainly on the modulation of the adenylyl cyclase pathway via pertussis toxin (PTX)-sensitive G proteins. To further investigate signaling of the human Mel 1a receptor, we have developed an antibody directed against the C terminus of this receptor. This antibody detected the Mel 1a receptor as a protein with an apparent molecular mass of approximately 60 kDa in immunoblots after separation by SDS-PAGE. It also specifically precipitated the 2-[125I]iodomelatonin (125I-Mel)-labeled receptor from Mel 1a-transfected HEK 293 cells. Coprecipitation experiments showed that G(i2), G(i3), and G(q/11) proteins couple to the Mel 1a receptor in an agonist-dependent and guanine nucleotide-sensitive manner. Coupling was selective since other G proteins present in HEK 293 cells, (G(i1), G(o), G(s), G(z), and G12) were not detected in receptor complexes. Coupling of the Mel 1a receptor to G(i) and G(q) was confirmed by inhibition of high-affinity 125I-Mel binding to receptors with subtype-selective G protein alpha-subunit antibodies. G(i2) and/or G(i3) mediated adenylyl cyclase inhibition while G(q/11) induced a transient elevation in cytosolic calcium concentrations in HEK 293 cells stably expressing Mel 1a receptors. Melatonin-induced cytosolic calcium mobilization via PTX-insensitive G proteins was confirmed in primary cultures of ovine pars tuberalis cells endogenously expressing Mel 1a receptors. In conclusion, we report the development of the first antibody recognizing the cloned human Mel 1a melatonin receptor protein. We show that Mel 1a receptors functionally couple to both PTX-sensitive and PTX-insensitive G proteins. The previously unknown signaling of Mel 1a receptors through G(q/11) widens the spectrum of potential targets for melatonin.
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PMID:Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins. 1059 79

We have previously shown that chronic alcohol consumption inhibits liver regeneration by impairing epidermal growth factor receptor (EGFR)-operated phospholipase C-(gamma1) (PLC-(gamma1)) activation and the resultant rise in intracellular [Ca(2+)](i). In hepatocytes, activation of PLC-(gamma1) by EGFR requires involvement of a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory protein (G(alphai)) as an intermediate. In the present study, we first identified the G(alphai) protein isoform associated with the activated EGFR, and then examined whether the toxic effect of alcohol on EGFR signaling and liver cell proliferation was exerted on this association. In cultured hepatocytes from control rats, EGF rapidly induced association between EGFR and G(alphai2) but not other G(alphai) isoforms. In hepatocytes from rats fed alcohol for 16 weeks, EGF failed to stimulate this association of G(alphai2) with the EGFR. The impairment of EGFR-G(alphai2) complex formation caused by alcohol was associated with a decreased level of G(alphai2) in the plasma membrane fraction (approximately 50% control). Pertussis toxin, an inhibitor of G(alphai) function, produced an analogous disruption of the association between G(alphai2) and the EGFR, as well as inhibiting EGF-induced DNA synthesis. It is concluded that, in hepatocytes, G(alphai2) is specific among G(alphai) isoforms in coupling activation of the EGFR to other signaling pathways that control cell proliferation. Impaired coupling of G(alphai2) of EGFR could contribute to the mechanism by which chronic alcohol exposure inhibits liver regeneration.
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PMID:Specific involvement of G(alphai2) with epidermal growth factor receptor signaling in rat hepatocytes, and the inhibitory effect of chronic ethanol. 1128 93

IL-15 induces proliferation, inhibits apoptosis and increases IL-4 production in murine mast cells. There is evidence that these activities are mediated via the uncharacterised receptor, IL-15R-X, rather than the classical three-chain IL-15 receptor. Effects of IL-15 on important aspects of mast cell biology, such as migration and degranulation, are unknown. We report that IL-15 induces migration of murine and human mast cells in a dose-dependent and biphasic manner, with peaks of migration occurring at approximately 10(-15) and approximately 10(-9) M. The potency of the response was similar to that induced by other well-established mast cell chemoattractants. Competition assays performed with murine and human mast cells indicate that both peaks of migration are due to chemotaxis. Pre-treatment of cells with pertussis toxin (PTX), a guanine nucleotide-binding regulatory protein (G-protein) inhibitor, resulted in complete inhibition of murine mast cell migration at approximately 10(-15) M IL-15, and human mast cell migration at approximately 10(-15) and approximately 10(-9) M. This demonstrates that murine and human mast cells express a PTX-sensitive receptor, activated in response to IL-15. Additionally, IL-15 did not induce degranulation in murine mast cells. Locally-produced IL-15 may contribute to mast cell recruitment during inflammatory responses, thereby acting as a linking cytokine between innate and adaptive arms of the immune system.
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PMID:IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor. 1604 40

Muscarinic acetylcholine receptor (mAChR)-mediated guanine nucleotide-binding regulatory protein (G protein) activation and the functional interaction between receptors and the respective G proteins were investigated using an agonist-induced [(35)S]guanosine-5'-O-(gamma-thiotriphosphate) ([(35)S]GTPgammaS)-binding approach in membranes of 3 native equine airway segments (trachea, bronchus and lung), which differ tremendously in mAChR density and subtype distribution; especially subtypes that couple negatively to adenylyl cyclase through G(i/0) proteins, i.e. M(2) receptors. The assay was initially optimized by determining the influence of incubation time, guanosine 5'-diphosphate (GDP), MgCl(2) and NaCl on basal and agonist-stimulated [(35)S]GTPgammaS binding. In standard assays, the presence of 10 mumol/l GDP, 10 mmol/l MgCl(2) and 200 mmol/l NaCl increased carbachol-induced specific [(35)S]GTPgammaS binding in a segment- and receptor-density-dependent manner. Hereby, mAChR agonists stimulated [(35)S]GTPgammaS binding with a rank order of potency (oxotremorine M > carbachol > acetylcholine), and in a specific segment- and receptor-density-dependent manner (trachea > bronchus > lung). The increase in the specific [(35)S]GTPgammaS binding was potently inhibited by the mAChR antagonist atropine. Pertussis toxin and N-ethylmaleimide as G(i/0) protein ADP-ribosylating and alkylating agents reduced basal and agonist-stimulated [(35)S]GTPgammaS binding. The mAChR-stimulated [(35)S]GTPgammaS binding serves as a useful method for investigating the functional interaction between mAChRs and their respective G proteins in native airway tissue membranes of equines.
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PMID:Segment-dependent activation of muscarinic acetylcholine receptor-mediated [35S]Guanosine-5'-O-(gamma-thiotriphosphate) binding in airway tissue membranes. 1929 55


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