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)

The effects of extracellular adenine and pyrimidine nucleotides on the acetylcholine-activated K+ channels (KACh) in rat cardiac myocytes were compared and examined by using the patch-clamp technique. In perforated-patch whole-cell recording experiments, extracellular adenosine triphosphate (ATP) reversibly caused an increase in K+ current. 8-Cyclopentyl-1,3-dipropylxanthine (CPX; 1 microM), a potent A1-adenosine-receptor antagonist, only partially antagonized the ATP-induced increase in K+ current, whereas glibenclamide (30 microM) had no effect. In cell-attached mode, adenosine and ATP activated single channels that had nearly identical conductance (29 pS) and open time (1.53 ms). These results suggest that adenosine and ATP can activate the same population of K+ channels. Uridine triphosphate (UTP; 100 microM) also caused an increase in steady-state K+ current. In cell-attached mode, the addition of UTP to the recording pipette solution (not in the bath solution) activated the channel current. The single-channel conductance and open time for UTP-induced channel current were 27 pS and 1.57 ms, respectively. These values were similar to those for the K+ channels activated by adenosine or ATP. The rank order of potency for the activation of KACh channels was adenosine = ATP > UTP. The addition of CPX (1 microM) to the pipette solution attenuated the ATP-induced channel activity by approximately 70% and fully prevented activation by AMPCPP, a less hydrolyzable ATP analog but did not cause any effect on UTP-induced channel activity. In pertussis toxin-treated cardiac myocytes, no any activity of UTP-induced KACh-channel current was observed. Our results demonstrate that extracellular ATP and UTP can directly activate KACh-channel current. This activation also was linked to pertussis toxin-sensitive G protein. The effect of extracellular ATP is mainly caused by the action on binding to A1-adenosine receptor, whereas the effect of extracellular UTP may be mediated possibly by P2u-purinergic (or 5'-nucleotide) receptor.
J Cardiovasc Pharmacol 1998 Feb
PMID:Activation of muscarinic K+ channels by extracellular ATP and UTP in rat atrial myocytes. 947 61

We demonstrate that the human endothelin-B (ETB) receptor incorporates [3H]palmitic acid. Mutation of three putative palmitoylated cysteine residues (amino acids 402, 403 and 405) in the carboxyl terminus into serine residues (C2/3/5S) completely prevented palmitoylation of ETB. When expressed in CHO cells, C2/3/5S was localized on the cell surface, retained high affinity for ET-1 and ET-3, and was rapidly internalized when bound to the ligand. However, unlike the wild-type ETB, C2/3/5S transmitted neither an inhibitory effect on adenylate cyclase nor a stimulatory effect on phospholipase C, indicating a critical role of palmitoylation in the coupling with G-proteins, regardless of the G-protein subtype. Truncation of the carboxyl terminus, including all or a part of the three cysteine residues, gave palmitoylation-negative and -positive deletion mutants, delta 402 and delta 403. Despite the absence of the cytoplasmic tail, both delta 402 and delta 403 showed essentially the same features as C2/3/5S, except that delta 403 did transmit a stimulatory effect on phospholipase C via a pertussis toxin-insensitive G-protein, most likely a member(s) of the Gq family. These results indicated a differential requirement for the carboxyl terminus downstream from the palmitoylation site in the coupling with G-protein subtypes, i.e., it is required for the coupling with Gi but not for that with Gq.
J Cardiovasc Pharmacol 1998
PMID:Cysteine residues in the carboxyl terminal domain of the endothelin-B receptor are required for coupling with G-proteins. 959 45

The mechanisms by which red wine polyphenolic compounds (RWPCs) induced endothelium-dependent relaxation were investigated in rat thoracic aorta rings with endothelium. RWPCs produced relaxation that was prevented by the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine-methyl-ester. This relaxation was abolished in the absence of extracellular calcium in the medium or in the presence of the Ca2+ entry blocker, La3+, but it was not affected by the nonselective K+ channels blocker, tetrabutylammonium. N-Ethyl-maleimide (NEM), a sulfhydryl alkylating agent, abolished vasorelaxation produced by RWPCs and acetylcholine but not that produced either by the sarcoendoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) pump inhibitor, cyclopyazonic acid (CPA) or the calcium ionophore, ionomycin. Neither pertussis toxin (PTX) nor cholera toxin (CTX) inhibited the vasorelaxant effect of RWPC. The effect of RWPC was not affected by the phospholipase C (PLC) blocker, L-alpha-glycerophospho-D-myo-inositol 4-monophosphate (Gro-pip), and the phospholipase A2 pathway blockers, quinacrine and ONO-RS-082. Finally, the protein kinase C (PKC) inhibitor, GF 109203X, and tyrosine kinase inhibitors, tyrphostin A-23 and genistein, did not impair the response to RWPCs. These results suggest that RWPCs produce endothelium-NO-derived vasorelaxation through an extracellular Ca2+-dependent mechanism via an NEM-sensitive pathway. They also show that PTX- or CTX-sensitive G proteins, activation of PLC or PLA2 pathways, PKC, or tyrosine kinase may not be involved.
J Cardiovasc Pharmacol 1999 Feb
PMID:Mechanism of endothelial nitric oxide-dependent vasorelaxation induced by wine polyphenols in rat thoracic aorta. 1002 33

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.
J Cardiovasc Pharmacol 2000 May
PMID:Cardiac swelling-induced chloride current is enhanced by endothelin. 1081 80

Modifications by atherosclerosis of endothelium-dependent and -independent relaxations were evaluated in carotid arteries isolated from Watanabe heritable hyperlipidemic (WHHL; age 20-29 months) and age-matched Japanese white (JW) rabbits. Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit arteries. Endothelium-dependent relaxations induced by acetylcholine, partly depressed by N(G)-nitro-L-arginine (L-NA), were significantly inhibited in the WHHL rabbit arteries with atherosclerosis, compared with those in the arteries without atherosclerotic lesions from JW and WHHL rabbits. No difference was observed in the relaxation caused by superoxide dismutase in these arteries. Conversely, endothelium-dependent relaxations by substance P were greater in the arteries with and without atherosclerosis from WHHL rabbits than in the arteries from JW rabbits. Endothelium-independent relaxations elicited by sodium nitroprusside and 2,2-(hydroxynitrosohydrazino)bis-ethanamine (NOC18) did not differ in the arteries from JW and WHHL rabbits. The responses to acetylcholine and substance P of JW rabbit arteries with the endothelium were not attenuated by treatment with pertussis toxin. L-NA-resistant, endothelium-dependent relaxations by substance P were almost abolished by charybdotoxin, and atherosclerosis did not alter the response. It is concluded that endothelial functions, evaluated by substance P, in rabbit carotid arteries are not impaired by atherosclerosis and by long exposure to hyperlipidemia in vivo. Dysfunction of muscarinic receptors may be involved in the depressed response to acetylcholine. As far as the arteries used in the present study are concerned, responses mediated possibly by endothelium-derived hyperpolarizing factor (EDHF) are unlikely to be modulated by atherosclerosis.
J Cardiovasc Pharmacol 2000 Nov
PMID:Comparison of endothelium-dependent relaxation in carotid arteries from Japanese white and Watanabe heritable hyperlipidemic rabbits. 1106 23

It has been demonstrated that brief periods of coronary artery occlusion before a prolonged period of sustained occlusion paradoxically protect the myocardium against infarction. The mechanisms involved in this phenomenon, termed "ischaemic preconditioning" (IPC) are still not clear, although it has been established that opioid receptors are involved. The aim of this study was to probe some of the plausible mechanisms involved in the phenomenon by using an in vivo model of myocardial infarction in intact rat, a model that allows electro-cardiographic and enzymatic in addition to morphometric evaluation of the development of 24-hour myocardial infarction. Selective opioid delta-receptor agonist (DADLE) and antagonist (natrindole), and opioid kappa-receptor agonist (U-50488H) and antagonist (nor-BNI) were used. To clarify some of the mechanisms of IPC, we used selective inhibitors of the anticipated cellular systems involved. Pertussis toxin (inhibitor of adenylate cyclase G(I/o) protein), glibenclamide (inhibitor of K(ATP ) channel) and chelerythrine (inhibitor of PKC) were used. Results obtained showed that: Both opioid delta- and kappa-receptors were involved in the beneficial effect of IPC, although we were unable to differentiate between opioid receptor subtypes (delta1, delta2 and kappa1, kappa2). Opioid delta- and kappa-receptors displayed different effects in IPC. After 30 minutes of left coronary occlusion and 2-hour reperfusion, opioid delta-receptor agonist DADLE significantly decreased (p < 0.05) the infarct size (by 66%--from % IS/AAR 59.80 in the control, untreated infracted rats to % 20.40), without a significant effect (p > 0.05) on the occurrence of early arrhythmias. Opioid kappa-receptor agonist U-50488H produced mainly antiarrhythmic effects. It decreased % IS/AAR by 44%, reduced the occurrence of early arrhythmias by 77%, and decreased ventricular ectopic beats by 80%. Both opioid delta- and kappa-receptor agonists significantly reduced (p < 0.05 ) early (2-hour) mortality by 22% and 19% respectively. The above opioid delta- and kappa-receptor cardiac effects were abolished by the use of respective specific opioid delta- and kappa-receptor antagonists. The beneficial effects of opioid delta- and kappa-receptor agonists persisted for at least 24 hours post-infarction. It is most likely that both opioid delta- and kappa-receptors act via common cellular mechanisms involving: activation of ATP-sensitive (sarcolemmal) K+ channel via G(I/o) proteins (based on the results of our experiments with K(ATP) channel antagonist, glibenclamide); phosphatidylinositol pathway via activation of protein kinase C (judging from the results of our experiments with the inhibitor of PKC, chelerythrine); and the recently proposed "cross talk" between beta (1)-adrenergic and opioid receptors in cardiac myocytes (involving inhibition of adenylate cyclase by G(I/o) proteins). Exploring the possibility of this signaling pathway will be the next step in our experimental studies.
Cardiovasc J S Afr
PMID:Mechanisms of opioid delta (delta) and kappa ( kappa) receptors' cardioprotection in ischaemic preconditioning in a rat model of myocardial infarction. 1274 44

Recently, we demonstrated that beta2AR and several other Galphas-coupled receptors in human atria also couple to Galphai, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Galphai in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Galphai. Right atrial appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82 +/- 18% more Galphai2 than atria from mature adults (P < 0.002); this increase in Galphai with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [32P]azidoanilido-GTP. We also find that receptor-mediated activation of Galphai is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Galphai with pertussis toxin, indicating that the age-dependent increases in Galphai expression and activation have functional consequences. Because beta2ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Galphai may have a role in depressing cardiac function in aged human atria.
J Cardiovasc Pharmacol 2003 Nov
PMID:Age increases expression and receptor-mediated activation of G alpha i in human atria. 1457 16

There has been much evidence showing that the central sympathetic nervous system may be involved in the control of blood pressure. In the present study, we investigated the role of the presynaptic alpha2-adrenergic receptors and the cyclic adenosine monophosphate-dependent protein kinase (protein kinase A) in the regulation of norepinephrine release in the central nervous system in hypertension. The alpha2-adrenergic receptor agonists UK 14, 304 and clonidine inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner in the medulla oblongata of Sprague-Dawley rats. Pretreatment of pertussis toxin (a potent inhibitor of the Gi-protein) attenuated the suppression of NE release by UK 14, 304. The protein kinase A inhibitor H-8 also reduced the stimulation-evoked [3H]norepinephrine release in rat medulla oblongata. In spontaneously hypertensive rats, the inhibitory effect of UK 14, 304 on the stimulation-evoked norepinephrine release was significantly less than in age-matched normotensive Wistar-Kyoto rats. By contrast, the protein kinase A inhibitor H-8 reduced the stimulation-evoked norepinephrine release to a greater extent in hypertension than in normotensive controls. The results of the present study showed that the alteration in the presynaptic alpha2-receptor-protein kinase A system might actively participate in the regulation of norepinephrine release in the central nervous system in hypertension.
J Cardiovasc Pharmacol 2003 Dec
PMID:Role of alpha2-adrenergic receptors and cyclic adenosine monophosphate-dependent protein kinase in the regulation of norepinephrine release in the central nervous system of spontaneously hypertensive rats. 1487 Oct 35

Adenosine A1-receptor-mediated inhibition of exocytotic norepinephrine (NE) release from sympathetic nerve endings has been implicated as an endogenous cardioprotective mechanism. So far, the intraneuronal signal transduction underlying the adenosine A1-receptor-elicited inhibition of NE release is not known. In the present study, we determined in isolated Langendorff-perfused rat hearts the role of inhibitory G-proteins and of adenylyl cyclase (AC) on NE release after pharmacologic adenosine A1-receptor activation. NE release was induced by electrical field stimulation and was assessed in the coronary effluent by high-performance liquid chromatography. Adenosine A1-receptor activation with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased NE release by approximately 50% in hearts from both untreated and pertussis toxin-pretreated rats. In hearts from untreated rats, suppression of NE release in response to CCPA was completely abolished by the cell-permeable AC inhibitor 9-(tetrahydro-2'-furyl)adenine (SQ 22536). Direct activation of AC with forskolin increased NE release by approximately 20%. In the presence of forskolin, stimulation of adenosine A1-receptors with CCPA or inhibition of AC with SQ 22536 decreased NE release to baseline. These findings suggest a Gi-protein-independent but AC-dependent inhibition of NE release following adenosine A1-receptor activation.
J Cardiovasc Pharmacol 2005 Jan
PMID:Adenylyl cyclase-dependent inhibition of myocardial norepinephrine release by presynaptic adenosine A1-receptors. 1561 71

We have previously demonstrated that endothelin-1 (ET-1)-induced extracellular signal-regulated kinase (Erk) activity via the ETB receptor (EDNRB) is mediated through two independent pathways, a protein kinase C-dependent pathway and a pertussis toxin (PTX)-sensitive pathway, in astrocytes. In this study, we showed that the molar potency of ET-1 to induce Erk activation was two orders of magnitude higher in dibutyryl cAMP (DBcAMP)-treated astrocytes than in quiescent astrocytes. This DBcAMP-enhanced molar potency of ET-1 in Erk activation was selectively inhibited by pretreatment of astrocytes with PTX. The expression level of EDNRB in astrocytes was markedly upregulated by DBcAMP-induced cytodifferentiation. However, this up-regulation was simply attributed to the high expression of low-affinity sites. The molar potency of ET-1 to induce both stimulation of inositol trisphosphate production and activation of protein kinase C in DBcAMP-treated astrocytes was similar to that in quiescent astrocytes. On the contrary, the molar potency of ET-1 to induce accumulation of Ras-GTP was two orders of magnitude higher in DBcAMP-treated astrocytes than in quiescent astrocytes, which was consistent with the case of ET-1-induced Erk activation. Moreover, the ET-1-induced Ras activation was PTX sensitive. These results suggest that cytodifferentiation selectively enhances the PTXsensitive Ras/Erk pathway induced by ET-1 in astrocytes, and that cytodifferentiation-induced EDNRB up-regulation might not contribute to this selective potentiation of ET-1 signaling.
J Cardiovasc Pharmacol 2004 Nov
PMID:Cytodifferentiation enhances Erk activation induced by endothelin-1 in primary cultured astrocytes. 1583 8


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