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)

To elucidate the mechanism(s) of altered responses of various receptors observed in asthma, we examined levels of G proteins in lung membranes isolated from guinea pigs at various stages of experimental asthma. We found that levels of Gi2 alpha and Gq alpha increase after multiple exposures to aerosolized antigen but not after a single exposure. Levels of Gi1 alpha, Gs alpha and G beta did not change under these experimental conditions. Tracheas from these animals exhibited hyperresponsive muscarinic bronchoconstriction and hyporesponsive beta adrenoceptor-mediated relaxation of endothelin-preconstricted tracheas as measured by an ex vivo isometric assay. No changes in numbers or affinities of membrane M3 muscarinic and beta-2 adrenergic receptors were detected as measured by binding of [3H]QNB and [125I]CYP, respectively. The impairment of beta adrenoceptor-mediated relaxation of tracheas isolated from animals treated by multiple challenges was reversed by the pretreatment of tracheas with pertussis toxin. On the other hand, the carbamylcholine-stimulated GTPase activity was higher in lung membranes isolated from animals in the multiple challenge group and was blocked by anti-Gq alpha protein antibody. Taken together, our present observations suggest that an underlying mechanism of altered receptor responses associated with asthma is in part due to increased expression of Gi2 alpha and Gq alpha proteins, leading to altered coupling of receptors to effector systems.
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PMID:Alteration of G protein levels in antigen-challenged guinea pigs. 799 89

Muscarinic acetylcholine receptors (mAChRs) mediate their main cardiac effects via pertussis toxin-sensitive G-proteins. Physiological effects differ considerably between atrium and ventricle, and it is unknown to which extent these differences derive from selective receptor-G-protein coupling or further downstream events. We have characterized specific coupling between mAChRs and Gi/Go-protein isoforms in atrial and ventricular myocardium by agonist-dependent photoaffinity labeling with [(32)P]azidoanilido GTP (aaGTP) and immunoprecipitation in sarcolemmal membranes from terminally failing human hearts. The total amount of mAChRs, as determined by specific binding of [(3)H]QNB, was significantly higher in right-atrial (RA +/- SEM, 959 +/- 68 fmol/mg, n = 4) than in left-ventricular membranes (LV, 582 +/- 53 fmol/mg, n = 6). Standardized immunoblots revealed that Gialpha-2 was the predominant subtype in both regions. A 40-kDa splice variant of Goalpha (Goalpha-1 and/or Goalpha-3) was almost exclusively detectable in RA. Levels of Gialpha-3 and a 39-kDa splice variant of Goalpha (Goalpha-2) were also higher in RA. Basal aaGTP binding was higher in RA than in LV for all Gialpha/Goalpha subtypes. The carbachol (10 micromol/l)-induced increase in aaGTP binding was significantly higher in RA than in LV for Goalpha-1/3 (336 +/- 95% of LV, n = 4) and for Gialpha-3 (211 +/- 83%), lower for Gialpha-2 (42 +/- 5%), and was similar in both regions for Goalpha-2 (130 +/- 62%). The differential coupling of mAChRs in human RA and LV suggests that the initiation of different physiological responses to mAChR stimulation starts with signal sorting at the receptor-G-protein level.
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PMID:Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium. 1451 34


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