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)

Activation of adrenoceptors of the alpha 2-subtype can cause an inhibitory or an excitatory response, depending on the cellular system affected. At the plasma membrane, where the extracellular signal is transduced via the alpha 2-adrenoceptor into an intracellular signal, only one transduction process has clearly been established until now by studies in various cellular systems, namely the inhibition of adenylate cyclase. The enzyme inhibition, which is caused by activation of alpha 2-adrenoceptors, is mediated by the inhibitory guanine nucleotide-binding regulatory component (Ni). This component serves as coupler between the activated alpha 2-adrenoceptor and the adenylate cyclase. Selective inactivation of Ni by pertussis toxin not only impairs the alpha 2-adrenoceptor-mediated adenylate cyclase inhibition but also the overall cellular response caused by activation of the receptors. It is suggested that Ni and the adenylate cyclase inhibition mediated by this regulatory protein is the major cellular transduction process following interaction of agonists with alpha 2-adrenoceptors.
J Cardiovasc Pharmacol 1985
PMID:Coupling mechanisms of alpha 2-adrenoceptors. 241 70

In strip preparations from the rabbit main pulmonary artery, it was not possible to differentiate convincingly between alpha 1- and alpha 2-adrenoceptors, when selective agonists such as methoxamine, St 587, B-HT 920, and clonidine, as well as selective antagonists such as prazosin and yohimbine were used for receptor characterization. Measurements of the membrane potential of the vascular smooth-muscle cells with intracellular glass micropipettes showed similar depolarizations in response to the alpha 1-selective methoxamine and the alpha 2-selective B-HT 920. These observations suggest the occurrence of a uniform alpha-adrenoceptor population in the rabbit main pulmonary artery. However, in contrast to alpha 1-agonists, contractile responses to alpha 2-agonists differed considerably in their dependence on external Ca, as revealed in Ca withdrawal experiments, as well as by the use of Ca antagonists. Furthermore, inactivation of the guanine nucleotide-binding inhibitory protein (Ni protein) by pertussis toxin impaired vasoconstriction, in response to alpha 2-agonists, but left that to alpha 1-agonists unaffected. It is suggested that alpha 1- and alpha 2-agonists induce two distinct conformational changes in an otherwise uniform alpha-adrenoceptor of the rabbit main pulmonary artery. By the mediation of Ni protein, alpha 2-agonists appear to allow influx of Ca into the vascular muscle cells through a type of Ca channel that is unlikely to be controlled by voltage.
J Cardiovasc Pharmacol 1986
PMID:Vascular smooth muscle: availability of calcium through alpha-adrenoceptor stimulation. 243 10

Exogenous GTP was required for the induction of Ca2+ release from smooth muscle SR by IP3 if endogenous GTP was depleted. NaN3 could function as a partial substitute for GTP as a cofactor for the IP3-induced Ca2+ release from the SR. In contrast to the IP3-induced Ca2+ release, caffeine-induced Ca2+ release from the SR did not require GTP. Pertussis toxin inhibited the IP3-induced Ca2+ release from the SR, whereas it had no effect on caffeine-induced Ca2+ release. These results indicate that in smooth muscle two different Ca2+ release-channels exist in the SR: (a) activated by IP3, and (b) activated by caffeine or Ca2+.
J Cardiovasc Pharmacol 1988
PMID:The specific GTP requirement for inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned vascular smooth muscle. 246 78

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)
Cardiovasc Res 1988 Feb
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

To determine the effects of exercise in experimental autoimmune myocarditis, guinea pigs immunised with heterologous heart protein (rat heart), Freund's complete adjuvant, and pertussis vaccine (treated group) were exercised on a treadmill for a total of 11 weeks and compared with non-exercise treated animals. In vivo heart rates and pressures, in vitro left ventricular pressure-volume relations, myocardial histology, circulating antiheart antibody, and in vitro lymphocyte stimulation were determined. Exercise resulted in increased cardiac dilatation in treated animals as assessed by in vitro left ventricular pressure-volume relations compared with non-exercise treated animals (at 8 mmHg 1.41(0.17) ml.kg-1 vs 1.20(0.17) ml.kg-1 respectively, p less than 0.005). Exercise also resulted in increased concentrations of circulating antiheart antibody as assessed by radioimmunoassay (0.14(0.04) microgram vs 0.10(0.03) microgram respectively, p = 0.01), and increased lymphocyte activation to specific antigen (stimulation index 3.7(0.07) vs 2.4(1.0) respectively, p less than 0.001). Despite the associated augmentation of autoimmunity with cardiac dilatation, there were no differences in the histopathological findings between the exercised treated and the non-exercised treated animals either qualitatively or quantitatively (number of inflammatory cell microaggregates). This finding suggests that, although the immune system is important in experimental autoimmune myocarditis, the amount of inflammation and necrosis does not appear to correlate with the degree of left ventricular dilatation and presumed dysfunction.
Cardiovasc Res 1987 Mar
PMID:Exercise induced augmentation of cellular and humoral autoimmunity associated with increased cardiac dilatation in experimental autoimmune myocarditis. 365 88

Male and female guinea pigs underwent immunisation with heterologous heart protein (rat heart), complete Freund's adjuvant and pertussis vaccine (immunised) or normal saline (control) at weekly intervals for 6 weeks, and were subsequently studied. In vivo intracardiac pressures, cardiac outputs, blood volumes, in vitro pressure-volume relations, left ventricular collagen contents, light microscopy, direct immunofluorescence, lymphocyte stimulation studies, and serology for circulating anti heart antibody (haemagglutination and radioimmunoassay) were performed. Immunised guinea pigs studied between 5 and 8 weeks following the immunisation protocol demonstrated a 44% increase in LVEDP (p less than 0.005), an increase in right atrial pressure (p less than 0.001), although no change in aortic pressure or cardiac output when compared with controls. Left ventricular weight was increased 20% (p less than 0.001), and in vitro left ventricular volume by 34% (at 8 mmHg distending pressure, p less than 0.001). Lung wet weight was increased 44% (p less than 0.005), and left ventricular collagen content increased 60% (p less than 0.001). Cultured lymphocytes from treated guinea pigs demonstrated a 1.5- to 4.5-fold (dependent upon proximity to last immunisation) increase in radiolabelled thymidine uptake when incubated with guinea pig heart protein compared to controls (p less than 0.001), and circulating anti guinea pig heart antibodies were detected by haemagglutination and radioimmunoassay. Histological examination of the left ventricles revealed inflammatory cell infiltration and myocyte increase to varying degrees in 15 of the 18 treated animals. We conclude that inflammatory, probably immune-mediated, chronic myocarditis can be produced in the guinea pig.
Cardiovasc Res 1985 Oct
PMID:Experimental autoimmune myocarditis in the guinea pig. 405 37

Endothelin acts via specific membrane-bound receptors through signal transduction pathways that include increases in intracellular free calcium and inositol triphosphate generation. Two endothelin receptors have been cloned. The ETA receptor is ET-1 selective, and the ETB receptor is isopeptide nonselective. Both receptor subtypes are widely distributed throughout the body, although ETA receptors predominate in vascular smooth muscle, whereas ETB receptors predominate in the brain. The presence of mixed receptor subtypes makes functional screening of subtype-specific analogues difficult. A eukaryotic expression vector was constructed by inserting the cloned coding region of the human ETB receptor downstream from the Rous sarcoma promoter. COS-7 cells were transfected with this construct, and cell lines were isolated with stably integrated copies of the relevant gene. One line, 1C7, was shown to specifically bind 125I-ET-1. Scatchard analysis indicated a Kd value of 8.8 pM and a Bmax value of 1.02 pM/mg. ET-1 stimulated phosphoinositide hydrolysis in a dose-dependent manner, as did ET-3, sarafotoxin 6c, and [1,3,13,15Ala]ET-1, whereas BQ123, a selective ETA receptor antagonist, did not inhibit the action of ET-1. The transfected receptor stimulates phosphoinositide (PI) hydrolysis via a pertussis-sensitive pathway. Pretreatment of the membrane from 1C7 cells with dithio-bis-nitrobenzoic acid (DTNB) a negatively charged, nonpenetrating agent capable of oxidizing sulfhydryl groups, and N-ethyl-maleimide (NEM), a penetrating agent that causes irreversible alkylation of sulfhydryl groups, significantly reduces Bmax but has no effect on Kd. In whole cells, DTNB pretreatment abolishes the ability of ET-1 to stimulate PI hydrolysis.
J Cardiovasc Pharmacol 1993
PMID:COS-7 cells stably transfected to express the human ETB receptor provide a useful screen for endothelin receptor antagonists. 750 82

The purpose of this study was to examine the hypothesis that the calcium channel blocker verapamil modulates catecholamine-induced arrhythmias in brain and to explore potential mechanisms of action. Wistar rats with catheters previously inserted in the lateral cerebral ventricle and femoral artery received verapamil 10 or 50 micrograms/kg or the diluent (intracerebroventricularly, i.c.v.) into the lateral cerebral ventricle. Epinephrine was infused to produce arrhythmias. Onset of ventricular arrhythmias, premature ventricular complexes (PVCs), occurred at a significantly (p < 0.05) higher epinephrine dose after the higher dose of verapamil. Development of fatal arrhythmias, mainly ventricular tachyarrhythmias, occurred at significantly (p < 0.05) higher epinephrine concentrations with verapamil 50 micrograms/kg i.c.v. as compared with controls. Comparison of the two enantiomers of verapamil (50 micrograms/kg i.c.v.) showed that S(-)verapamil had the same effect as the racemic mixture whereas R(+)verapamil was intermediate between the control and S(-)verapamil. The antiarrhythmic action of verapamil could not be explained by alteration of the blood pressure (BP) response to epinephrine. Endogenous opioids were implicated in this action of verapamil because the (-)enantiomer of naloxone, which is an opioid antagonist, significantly (p < 0.05) antagonized the antiarrhythmic effects of centrally administered verapamil to suppress epinephrine-induced arrhythmias. In contrast the (+)enantiomer of naloxone did not alter verapamil-induced increase in arrhythmia threshold. Pretreatment with pertussis toxin i.c.v. antagonized the effects of verapamil. Verapamil did not alter the cyclic AMP response to isoproterenol in lymphocytes isolated from Wistar rats not exposed to any other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 May
PMID:Verapamil has antiarrhythmic effects that are mediated in brain through endogenous opioids. 752 66

In spontaneously hypertensive rats (SHR), cardiac adenylate cyclase is desensitized owing to down-regulation of myocardial beta-adrenoceptors and an increase in Gi alpha. We wished to determine whether these biochemical alterations in the beta-adrenoceptor-adenylate cyclase system precede development of hypertensive cardiac hypertrophy or whether this increase occurs only in later stages of the syndrome and represents a secondary phenomenon. Myocardial samples from 5- and 13-week-old SHR and age-matched Wistar Kyoto rats (WKY) as controls were studied. Cardiac beta-adrenoceptors were studied with [125I]cyanopindolol ([125I]ICYP] as radiolabeled ligand. beta-Adrenoceptor subtypes were determined with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. Gi alpha proteins were measured with the pertussis toxin-catalysed [32P]ADP ribosylation. Myocardial norepinephrine (NE) content was investigated with high pressure liquid chromatography. In myocardial membranes of 13-week-old SHR, the number of total beta-adrenoceptors as well as beta 1- and beta 2-adrenoceptors was reduced. No difference was observed between SHR and WKY, at age 5 weeks. The nonionic detergent Lubrol PX at 0.5% (vol/vol) increased the amount of detectable Gi alpha by a factor of 14. Under these optimal conditions, Gi alpha was increased by 30% in 13-week-old SHR, but not 5-week-old SHR as compared with WKY. Myocardial NE content was increased by 25-35% in both 5- and 13-week-old SHR as compared with WKY. The results showed that nonspecific beta-adrenoceptor downregulation and an increase in Gi alpha occurs in hypertensive cardiac hypertrophy of SHR. In the prehypertensive stage, these changes were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 Jun
PMID:Cardiac norepinephrine, beta-adrenoceptors, and Gi alpha-proteins in prehypertensive and hypertensive spontaneously hypertensive rats. 752 91

Angiopeptin (AP: BIM23014C), a cyclic analogue of the peptide hormone somatostatin, inhibits intimal hyperplasia after balloon angioplasty. This inhibition has been attributed to a direct inhibitory effect on smooth muscle cell (SMC) proliferation. However, the SMC that proliferate in the intima and contribute to intimal hyperplasia arrive there by migrating from the injured media, suggesting that SMC migration may also play an important role in this process. Indeed, in the experiments we describe, AP inhibited the migration of rat aortic SMC cells (RA-SMC) in response to type I collagen, the predominant form of collagen in the vessel media, and did so dose dependently. RA-SMC migration was inhibited 70% in the presence of AP 100 nM. RA-SMC adhesion to type I collagen in these conditions was not inhibited, suggesting that AP does not interfere with RA-SMC recognition of type I collagen; instead, it blocks subsequent signaling events that are necessary for RA-SMC migration in response to type I collagen. AP inhibited the forskolin-stimulated accumulation of cyclic AMP by RA-SMC (35% at 30 nM). In addition, pertussis toxin (PT), which blocks Gi-mediated inhibition of adenylyl cyclase, blocked the inhibitory effect of AP on cyclic AMP (cAMP) accumulation and also blocked the inhibitory effect of AP on RA-SMC migration. These findings suggest that the inhibitory effect of AP on intimal hyperplasia is due at least in part to its effects on SMC migration and that these effects are mediated by a Gi-dependent pathway and may involve inhibition of adenylyl cyclase and cAMP accumulation.
J Cardiovasc Pharmacol 1995 Apr
PMID:Angiopeptin (BIM23014C) inhibits vascular smooth muscle cell migration in vitro through a G-protein-mediated pathway and is associated with inhibition of adenylyl cyclase and cyclic AMP accumulation. 759 30


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