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 coupling of the human coronary adenosine receptor to a G protein was investigated in vitro. Hearts were obtained from accidental death victims and the left anterior descending coronary artery (LAD) was taken for experimentation. Cholera toxin (CT) and pertussis toxin (PT) ADP-ribosylated proteins with Mr of 45, 49 (CT), and 41 (PT) kDa. Both processes were sensitive to GTP gamma S. In LAD rings contracted with KCl, adenosine (ADO) and its analogs 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) produced concentration-dependent relaxation. These concentration-response curves were shifted to the right significantly in the presence of the competitive ADO receptor antagonist, 8-phenyltheophylline (8-PT), indicating the involvement of ADO receptors. Treatment with NaF/AlCl3, which uncouples G protein-mediated responses, caused significant attenuation of the relaxation responses to ADO, NECA, and CAD. When the rings were incubated with CT, there was an attenuation of the relaxations produced by ADO, CAD, NECA, and isoproterenol (ISOP). Incubation with PT resulted in significant inhibition of the relaxations induced by ADO, NECA, and CAD. The results provide evidence for the presence of CT- and PT-sensitive G protein(s) subserving the relaxing adenosine receptors in human coronary artery.
 ...
PMID:G proteins subserve relaxations mediated by adenosine receptors in human coronary artery. 172 66

The effects of adenosine and the adenosine receptor agonist (-)-N(6)-phenyl-isopropyladenosine (PIA) in the presence of isoprenaline on isometric force of contraction and calcium dependent slow action potentials were studied in papillary muscles from guinea pigs pretreated with pertussis toxin and control guinea pigs. Hearts from guinea pigs treated in the same way with pertussis toxin or solvent alone underwent histological examination. For comparison, hearts from isoprenaline treated guinea pigs were also studied. Pertussis toxin specifically inactivates guanine nucleotide binding proteins (N proteins) involved in transmembrane signal transduction in many receptor systems (for example, adenosine receptors, m-cholinoceptors, and and alpha 2 adrenoceptors). In papillary muscles from control guinea pigs adenosine and PIA in the presence of isoprenaline produced a negative inotropic effect and inhibited the maximal rate of depolarisation of slow calcium dependent action potentials in potassium depolarised papillary muscles. After pretreatment with pertussis toxin the inhibitory effects both on force of contraction and on the maximal rate of depolarisation of adenosine and PIA were abolished. Treatment with pertussis toxin produced disseminated myocardial necrosis and a disseminated cellular calcium overload evidenced by glyoxal-2-bis-hydroxyanil (GBHA) staining. Similar lesions (for example, myocardial necrosis and cellular calcium overload) were also observed after treatment with isoprenaline. In controls neither myocardial necrosis nor cellular calcium overload was found. It is concluded that pertussis toxin sensitive N proteins are involved in the inhibitory effects of adenosine and PIA on force of contraction and on slow calcium inward current during beta adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of the effects of adenosine on force of contraction and the slow calcium inward current by pertussis toxin is associated with myocardial lesions. 316 39

Adenosine and acetylcholine exert negative chronotropic and anti-adrenergic effects on nonischemic myocardium presumably via receptor coupling to the same or similar inhibitory guanine nucleotide binding protein (Gi). To determine whether the cardioprotective effect of adenosine is mediated via adenosine A1 receptor coupling to Gi proteins, isolated rat hearts, perfused at constant pressure and constant heart rate, were subjected to 30 min global normothermic (37 degrees C) ischemia and 45 min reperfusion. Untreated control hearts recovered 52 +/- 2% of preischemic left ventricular developed pressure (LVDP). Hearts treated for 10 minutes prior to ischemia with adenosine (100 microM) and the adenosine A1 receptor agonist cyclohexyladenosine (CHA, 0.25 microM) recovered 67 +/- 4% and 70 +/- 4%, respectively. Hearts treated with the non-specific muscarinic cholinergic agonist carbamylcholine (1 microM) exhibited similar enhanced postischemic recovery (70 +/- 3%). Pretreatment of rats with pertussis toxin (25 micrograms/kg i.p., 48 h prior to isolation) significantly reduced the negative chronotropic effects of adenosine and CHA. Pertussis toxin pretreatment also blocked the beneficial effects of adenosine (57 +/- 4% recovery) and CHA (49 +/- 4% recovery) on postischemic function. These results support the hypothesis that the salutary effect of adenosine on the ischemic myocardium is mediated via adenosine A1 receptor coupling to a pertussis toxin sensitive G protein, presumably Gi.
 ...
PMID:Pertussis toxin blocks adenosine A1 receptor mediated protection of the ischemic rat heart. 823 Feb 43

Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry weight, respectively). Addition of the adenosine A1 receptor agonist R-phenylisopropyl adenosine before and during Ca2+ PD provided protection similar to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist, 8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC-mediated protection was aborted when hearts subjected to CPC were treated with pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present study suggests that Ca2+ preconditioning confers significant protection against the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result from adenosine release during preconditioning and by Gi-protein-modulated mechanisms.
 ...
PMID:Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury in rat heart. Role of adenosine. Fixed. 829 74

Patients with high serum immunoglobulin E levels were reported to be protected against sudden death during acute myocardial infarction. The protection mechanism might be attributed to the facilitation of histamine release from sensitized mast cells; however, this remains to be clarified. In this study, we examined the influence of sensitization on ventricular fibrillation (VF) induced by myocardial hypoxia/reoxygenation (H/R). Guinea pigs were actively sensitized by subcutaneous injection of ovalbumin in Bordetella pertussis vaccine. Hearts isolated from non-sensitized and sensitized guinea pigs were subjected to 30-min hypoxia / 30-min reoxygenation using a Langendorff apparatus. The amount of histamine released in the sensitized guinea-pig hearts was elevated, and the duration of VF was found to be reduced. The treatment with a histamine H2-receptor antagonist inhibited the reduction of VF duration. Treatment of the non-sensitized hearts with the histamine H2-receptor agonist resulted in the decrease of VF duration to the same level as that in the sensitized hearts. In conclusion, these results suggest that the risk of sudden death during myocardial H/R may be attenuated in the sensitized hearts and that histamine H2-receptor activation due to the released histamine may be involved in the protective effect.
 ...
PMID:The protective effect of H2-receptor activation against the duration of myocardial hypoxia/reoxygenation-induced ventricular fibrillation in sensitized guinea-pig hearts. 1634 Jan 55