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)

Whole cell currents were recorded in cultured rat hippocampal neurons using the patch-clamp method. When the cells were held near the resting membrane potential (-60 mV) the application of adenosine (1 microM) or the adenosine analogues 2CA (100 nM) and R-PIA (40 nM) induced a steady-state inward current. This response was unchanged when extra- and intracellular media were used, in which Na+ and K+ were substituted by impermeable ions in equimolar concentrations. In contrast the current was affected by lowering the extracellular Cl- concentration and thus Cl- was considered to be the ionic carrier. Additionally an almost complete block of the current was observed after applications of DIDS (50 microM), a putative Cl- channel blocker. The modulated current was voltage-dependent and was slowly activated by hyperpolarizing voltage steps. The adenosine action was theophylline- and pertussis toxin-sensitive indicating that the modulatory effect is mediated via an A1 receptor coupled to a G protein of the Gi or Go class.
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PMID:Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons. 217 37

In C6 glioma cells, extracellular ATP and other nucleotide analogs stimulated phosphoinositide (PI) breakdown and inhibited isoproterenol-induced cyclic AMP (cAMP) accumulation. The rank orders of potencies of 15 nucleotide analogs for both responses were clearly different. ATP and adenosine 5'-O-(3-thiotriphosphate) are the most potent agonists for stimulating PI hydrolysis; 2-methylthio-ATP (2-MeSATP) is the most potent agonist for inhibiting cAMP accumulation. P1-mediated responses of PI turnover and cAMP formation are not present in C6 glioma cells. Pertussis toxin (PTX) blocked the nucleotide-induced inhibition of cAMP accumulation but exerted no effect on inositol phosphate formation. Short-term treatment with phorbol 12-myristate 13-acetate inhibited both signal transduction pathways. The effects of three P2 purinergic antagonists, suramin, reactive blue and 4,4'-diisothiocyanatostilbene sulfonic acid (DIDS), on ATP- and 2-MeSATP-induced stimulation of PI turnover and inhibition of cAMP formation, respectively, were compared. For stimulating PI turnover, suramin is a competitive antagonist (pA2, 4.4); reactive blue and DIDS are noncompetitive antagonists at 30 microM and 100 microM, respectively. For the inhibition of cAMP formation, reactive blue and DIDS competitively antagonized the response of 2-MeSATP (pA2 values, 6.3 for reactive blue and 5.7 for DIDS); suramin was only slightly effective at 100 microM. It was concluded that the nucleotide receptor is linked to phospholipase C by a PTX-insensitive Gp protein and the P2Y receptor is linked to adenylyl cyclase by a PTX-sensitive Gi protein. Suramin is a competitive antagonist for the nucleotide receptor; reactive blue and DIDS are more selective antagonists for the P2Y receptor.
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PMID:Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma cells. 801 79

Endothelins (ETs) are a family of peptide hormones that act on G protein-coupled ET(A) and ET(B) receptors. ETs exert inotropic and chronotropic actions in the heart. Myocardial ischemia is associated with increased plasma levels of ET and cell swelling. We examined the effect of ETs on dog atrial swelling-induced chloride current (I(Cl,swell)). Whole-cell patch clamp was used; 10 nM ET-1 or ET-2 increased I(Cl,swell) by approximately twofold. ET-2 had no effect if I(Cl,swell) activation was prevented by hypertonic superfusate. Outward ET-2-induced current was blocked by 150 microM DIDS more effectively than inward current. Overnight pretreatment with phorbol 12-myristate 13-acetate (1.6 microM), pertussis toxin (100 ng/ml), or dialysis of the cell with 300 microM 2'-deoxyadenosine 3'-monophosphate, a P-site inhibitor of adenylyl cyclase, did not diminish the effect of ET-2. The effect of ET-2 was blocked by an ET(A1)- (BQ123), but not an ET(B)-selective (BQ788) antagonist. ET-2-induced currents were inhibited approximately 70% by PD 98059 (30 microM), a selective MAPK kinase (MEK) blocker. PD 98059 did not affect basal whole cell current or I(Cl,swell) before exposure to ET-2. The data suggest that MEK activity is not required for activation of atrial I(Cl,swell) but that ET-2 stimulates I(Cl,swell) by a MEK-dependent pathway.
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PMID:Cardiac swelling-induced chloride current is enhanced by endothelin. 1081 80

We have previously shown that an ecto-NPPase modulates the ATP- and ADP-mediated P2Y(AC)-receptor activation in rat C6 glioma. In the present study, 2MeSADP and Ap(3)A induced no detectable PI turnover and were identified as specific agonists of the P2Y(AC)-receptor with EC(50) values of 250 +/- 37 pM and 1 +/- 0.5 microM, respectively. P2Y(AC)-receptor stimulation increased MAP kinase (ERK1/2) activation that returned to the basal level 4 h after stimulation and was correlated with a gradual desensitization of the P2Y(AC)-purinoceptor. The purinoceptor antagonists DIDS and RB2 blocked MAP kinase activation. An IP(3)-independent Ca(2+)-influx was observed after P2Y(AC)-receptor activation. Inhibition of this influx by Ca(2+)-chelation, did not affect MAP kinase activation. Pertussis toxin, toxin B, selective PKC-inhibitors and a specific MEK-inhibitor inhibited the 2MeSADP- and Ap(3)A-induced MAP kinase activation. In addition, transfection with dominant negative RhoA(Asn19) rendered C6 cells insensitive to P2Y(AC)-receptor-mediated MAP kinase activation whereas dominant negative ras was without effect. Immunoprecipitation experiments indicated a significant increase in the phosphorylation of raf-1 after P2Y(AC)-receptor activation. We may conclude that P2Y(AC)-purinoceptor agonists activate MAP kinase through a G(i)-RhoA-PKC-raf-MEK-dependent, but ras- and Ca(2+)-independent cascade.
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PMID:Agonists of the P2Y(AC)-receptor activate MAP kinase by a ras-independent pathway in rat C6 glioma. 1157 41

In perfused rat liver, hypoosmotic exposure (225 mosmol/L) leads to a volume-regulatory decrease by release of K(+), Cl(-) and HCO(3)(-) through Ba(2+)-, DIDS- and quinidine-sensitive ion channels. The underlying signal transduction mechanisms, however, are unknown. As hypoosmotic hepatocyte swelling leads to a rapid activation of extracellular signal regulated kinases (Erks) and of p38(MAPK), the role of mitogen-activated protein kinases (MAPK) and PI-3-kinase in mediating the RVD in perfused rat liver was studied. The presence of the MEK inhibitor PD 098 059, which blocks the hypoosmotic activation of Erks, had no effect on the extent and time course of cell volume regulatory K(+) efflux. However, inhibitors of p38(MAPK) such as SB 203 580 and PD 169 316, but not their inactive analogue SB 202 474, significantly delayed and diminished the volume-regulatory K(+) efflux. Accordingly, in presence of these p38(MAPK) inhibitors, the hepatocytes remained in a more swollen state after completion of RVD. Inhibition of hypoosmotic Erk activation by pertussis or cholera toxin, erbstatin or genistein had no effect on RVD by hypoosmolarity. Likewise, neither inhibition of PI-3-kinase by wortmannin or LY 294 002 nor inhibition of S 6 phosphorylation by rapamycin nor protein kinase inhibition by H-7, H-89 or KT 5823 led to a significant change of RVD upon hypoosmolarity. The amount and time course of K(+) release by oxidative stress upon addition of t-BOOH or H(2)O(2) remained unaffected by inhibition of p38(MAPK) by SB 203 580, suggesting a specific inhibition of RVD-dependent K(+) release by this inhibitor. The findings suggest that swelling-induced activation of p38(MAPK), but not of Erks and PI-3-kinase, is involved in RVD in liver, whereas p38(MAPK) is apparently not involved in the net K(+) release induced by oxidative stress.
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PMID:Role of p38(MAPK) in cell volume regulation of perfused rat liver. 1183 54

Purinergic stimulation of airway epithelial cells induces Cl- secretion and modulates Na+ absorption by an unknown mechanism. To gain insight into this mechanism, we used a perfused micro-Ussing chamber to assess transepithelial voltage (V(te)) and amiloride-sensitive short-circuit current (I(sc-Amil)) in mouse trachea. Exposure to apical ATP or UTP (each 100 micromol/l) caused a large initial increase in lumen negative V(te) and I(sc), corresponding to a transient Cl- secretion, while basolateral application of ATP/UTP induced only a small secretory response. Luminal, but not basolateral, application of nucleotides was followed by a sustained and reversible inhibition of I(sc-Amil) that was independent of extracellular Ca2+ or activation of protein kinase C and was not induced by carbachol (100 micromol/l) or the Ca2+ ionophore ionomycin (1 micromol/l). Removal of extracellular Cl- or exposure to 200 microM DIDS reduced UTP-mediated inhibition of I(sc-Amil) substantially. The phospholipase inhibitor U73122 (10 micromol/l) and pertussis toxin (PTX; 200 ng/ml) both attenuated UTP-induced Cl- secretion and inhibition of I(sc-Amil). Taken together, these data imply a contribution of Cl- conductance and PTX-sensitive G proteins to nucleotide-dependent inhibition of the amiloride-sensitive Na+ current in the mouse trachea.
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PMID:Mechanisms for the inhibition of amiloride-sensitive Na+ absorption by extracellular nucleotides in mouse trachea. 1197 35

The intracellular signalling pathways and molecular mechanisms responsible for P2-purinoceptor-mediated chloride (Cl(-)) currents (I(Cl,ATP)) were studied in mouse ventricular myocytes. In standard NaCl-containing extracellular solutions, extracellular ATP (100 microm) activated two different currents, I(Cl,ATP) with a linear I-V relationship in symmetrical Cl(-) solutions, and an inwardly rectifying cation conductance (cationic I(ATP)). Cationic I(ATP) was selectively inhibited by Gd(3+) and Zn(2+), or by replacement of extracellular NaCl by NMDG; I(Cl,ATP) was Cl(-) selective, and inhibited by replacement of extracellular Cl(-) by Asp(-); both currents were prevented by suramin or DIDS pretreatment. In GTPgammaS-loaded cells, I(Cl,ATP) was irreversibly activated by ATP, but cationic I(ATP) was still regulated reversibly. GDPbetaS prevented activation of the I(Cl,ATP,) even though pertussis toxin pretreatment did not modulate I(Cl,ATP). These results suggest that activation of I(Cl,ATP) occurs via a G-protein coupled P2Y purinergic receptor. The I(Cl,ATP) persistently activated by GTPgammaS, was inhibited by glibenclamide but not by DIDS, thus exhibiting known pharmacological properties of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. In ventricular cells of cftr(-/-) mice, extracellular ATP activated cationic I(ATP), but failed to activate any detectable I(Cl,ATP). These results provide compelling evidence that activation of CFTR Cl(-) channels in mouse heart are coupled to G-protein coupled P2Y purinergic receptors.
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PMID:P2Y purinergic receptor regulation of CFTR chloride channels in mouse cardiac myocytes. 1497 3

The aim of this study was to characterize the effects of hypotonicity on the activity of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in human retinal pigment epithelial (RPE R-50) cells. Effects of hypotonicity on ion currents were investigated with the aid of the patch-clamp technique. A regulatory volume decrease in response to a hypotonic solution (200 mOsm/L) was observed that could be blunted by paxilline. In whole-cell current recordings, a hypotonic solution (200 mOsm/L) reversibly increased the amplitude of K+ outward currents (I(K)). The increase of I(K) could be reversed by iberiotoxin (200 nM), paxilline (1 microM), or tetrandrine (5 microM), but not by glibenclamide (10 microM), disulphonic acid (DIDS) (100 microM), or dequalinium dichloride (10 microM). In RPE R-50 cells pretreated with thapsigargin, aristolochic acid, or pertussis toxin, the increased amplitude of I(K) in response to hypotonicity was unaltered. In cell-attached patches, an increase in BK(Ca)-channel activity was observed during hypotonicity-induced cell swelling. The enhanced channel activity elicited under this condition was mainly mediated by an increase in the number of long-lived openings. These findings support the evidence for the coupling of volume swelling to the functional activity of BK(Ca) channels.
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PMID:The influence of hypotonicity on large-conductance calcium-activated potassium channels in human retinal pigment epithelial cells. 1568 15