UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the in vitro effect of sodium saccharin (NaSacch) on the rat adipocyte adenylyl cyclase complex. NaSacch (2.5-50 mM) inhibited significantly in a dose-dependent manner basal and isoproterenol-stimulated cAMP accumulation on isolated rat adipocytes. Similarly, NaSacch (2.5-50 mM) inhibited forskolin-stimulated adenylyl cyclase activity measured in the presence of Mg(2+)-ATP on adipocyte, astrocyte and thyrocyte membrane fractions. In contrast, NaSacch did not inhibit but slightly increased the forskolin-stimulated adenylyl cyclase activity measured in the presence of Mn(2+)-ATP and GDP beta S, a stable GDP analogue. The effect of NaSacch was not mediated through either the A1-adenosine receptor (A1R) or the alpha 2-adrenergic receptor (alpha 2AR). The inhibitory effect of NaSacch was additive to that of A1R agonist and was not blocked by the addition of the alpha 2AR antagonist RX 821002. Pretreatment of adipocytes with pertussis toxin slightly attenuated but did not abolish the inhibitory effect of NaSacch on forskolin-stimulated adenylyl cyclase activity on membrane fractions. These data suggest that the inhibitory effect of NaSacch on forskolin stimulated-adenylyl cyclase in adipocytes does not imply only Gi protein but also other direct or indirect inhibitory pathway(s) which remain to be determined.
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PMID:Sodium saccharin inhibits adenylyl cyclase activity in non-taste cells. 937 24

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.
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PMID:Activation of muscarinic K+ channels by extracellular ATP and UTP in rat atrial myocytes. 947 61

1. The effects of alpha1 adrenoceptor blocking agents doxazosin, indoramin, 5-methylurapidil, niguldipine, WB-4101 and chloroethylclonidine (CEC) on the force of contraction (Fc), velocity of contraction (+dF/dt) and relaxation (-dF/dt) of guinea pig papillary muscles were studied. 2. All examined substances were applied in a wide concentration range (0.01-30.0 microM) for at least 30 min at each concentration. Only alpha1a blockers [i.e., niguldipine (0.01-0.3 microM), 5-methylurapidil (1-30 microM) and WB-4101 (1-30 microM)] showed a concentration-dependent negative inotropic action. 3. This effect was significantly attenuated in the presence of glibenclamide (1 microM) and almost completely abolished by 1,3-dipropyl-8-p-sulfophenylxanthine (1 microM), an antagonist of adenosine receptors with a slight selectivity for the A1 subtype. 4. Pretreatment with dibenamine, an irreversible blocker of alpha1 adrenoceptors (0.6 microM for 40 min), abolished this effect, whereas pretreatment with CEC, an irreversible blocker of alpha1b adrenoceptors (1 microM for 20 min), and pertussis toxin (10 microg/kg IP, 4 to 5 days before experiments) diminished it. 5. The alpha1a adrenoceptor blocking agents in the presence of the unblocked alpha1b adrenoceptor trigger the negative inotropic action, which seems to include adenosine receptor stimulation and activation of ATP-sensitive K+ channels (K[ATP]) through an inhibitory G protein.
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PMID:Negative inotropic action of alpha-1a adrenoceptor blocking agents: role of adenosine and ATP-sensitive K+ channels. 951 86

The purpose of this study was to investigate the mechanisms by which adenosine stimulates proliferation of osteoblast-like cells, MC3T3-E1. Adenosine by itself induces the stimulation of cell proliferation and accentuates the mitogenecity of PDGFs (AA and BB homodimers) for the cells. 8-Cyclopentyl-1,3-dimethylxanthine (CPX), a nonselective adenosine receptor antagonist, partially inhibited adenosine-induced DNA synthesis in a competitive manner, suggesting that the mitogenic action of adenosine is, at least in part, mediated by xanthine-sensitive receptors. In pertussis-toxin (PTX)-pretreated cells, adenosine- but not PDGF-BB-stimulated DNA synthesis was partially inhibited, and CPX did not exert a further inhibitory effect, suggesting an involvement of PTX-sensitive G-protein downstream of CPX-sensitive receptor. When adenosine uptake was prevented with dipyridamole, the stimulation of proliferation by adenosine was not decreased at all, indicating that the CPX-insensitive part of adenosine action is not associated with the uptake of adenosine and subsequent incorporation into the nucleotide pool. Adenosine did not influence the basal level or the PDGF-BB-induced increase in [Ca2+]i. Since it is known that the cAMP pathway acts in inhibiting osteoblast proliferation, the mitogenic action of adenosine would be dependent on neither the cAMP pathway nor the phospholipase C/Ca2+ pathway. It has been concluded that adenosine exerts a mitogenic effect via two pathways at least, one mediated by xanthine-sensitive receptor and PTX-sensitive G-protein and the other through an unknown xanthine- and PTX-insensitive process.
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PMID:Mitogenic action of adenosine on osteoblast-like cells, MC3T3-E1. 954 19

Cell motility is an essential component of tumor progression and metastasis. A number of factors, both autocrine and paracrine, have been found to influence cell motility. In the present study, adenosine and adenine nucleotides directly stimulated chemotaxis of A2058 melanoma cells in the absence of exogenous factors. Three adenosine receptor agonists stimulated motility in the melanoma cells and two adenosine receptor antagonists strongly inhibited the chemotactic response to both adenosine and AMP. The chemotactic stimulation by adenosine and AMP was pertussis toxin sensitive. Otherwise unresponsive Chinese hamster ovary cells which were transfected with the adenosine A1 receptor cDNA acquired the direct, pertussis toxin sensitive, chemotactic response to adenosine, and this response was inhibited by adenosine receptor antagonists. These findings demonstrate that adenosine and adenine nucleotides are capable of stimulating chemotaxis of tumor cells mediated through an adenosine receptor, probably of the A1 subtype. The possibility of antimetastatic therapies based on inhibition of adenosine receptor activity is raised.
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PMID:Adenosine receptor mediates motility in human melanoma cells. 961 7

Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding G(i/o) proteins we examined the influence of pertussis toxin on the effects of the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benz eneacetamide (U-50,488) methanesulphonate and on the as yet undescribed effects of the opioid peptide dynorphin A (1-8) on contraction. In isolated, electrically driven, rat ventricular cardiomyocytes both agents concentration dependently reduced cell shortening within 15 min, decreasing the contractile response by 79+/-4% (n=5) and 62+/-2% (n=6) of control values at maximal effective concentrations of 10 microM (U-50,488) and 1 microM [dynorphin A (1-8)], respectively. Pertussis toxin pre-treatment (200 ng/ml; 4.5-5 h) completely abolished the effects of U-50,488 and dynorphin A (1-8) on the contractile response, indicating that these effects are mediated via G(i/o) proteins. In addition, the non-selective opioid receptor antagonist (-)-naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1-8) on the contractile response. Furthermore, the mu- and delta-opioid receptor agonist (D-Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results indicate that the decrease in cell shortening is due to stimulation of kappa-opioid receptors. The direct effect of kappa-opioid receptor agonists on the contractile response thus represents an additional mechanism for decreasing cardiac contractility, besides the M-cholinoceptor- or adenosine receptor-mediated pathway. It is conceivable that increased release of endogenous dynorphins from the heart during hypoxia may protect the heart in a similar manner to adenosine.
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PMID:Diminution of contractile response by kappa-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein. 977 24

1. Pharmacological studies have suggested that A3 receptors are present on central neurons. Recently this adenosine receptor subtype has been identified in the rat and its presence in the central nervous system has been confirmed. 2. In this study we investigated the effects of acute intracerebroventricular (i.c.v.) injections of N6-2-(4-aminophenyl)-ethyladenosine (APNEA), a non-selective A3 adenosine receptor agonist, on arterial blood pressure (ABP) and heart rate (HR), after treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of A1 adenosine receptors. 3. Anaesthetized rats, after DPCPX (12 microg(-1) kg i.c.v.), were treated with APNEA (0.4-4 microg kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arterial blood pressure without a change in heart rate. APNEA also induced hypotensive responses after i.c.v. pretreatment with aminophylline, at a dose of 20 microg kg(-1). In contrast, pretreatment 48 h before, with 4 microg kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effect induced by APNEA. Administration of APNEA at a higher dose (20 microg kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mmHg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1). Transection of the spinal cord abolished this significant fall in ABP, but not the decrease of HR. 4. These results suggest that a population of A3-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.
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PMID:The role of A3 adenosine receptors in central regulation of arterial blood pressure. 980 24

1. The effects of adenosine receptor agonists upon phenylephrine-stimulated contractility and [3H]-cyclic adenosine monophosphate ([3H]-cyclic AMP) accumulation in the cauda epididymis of the guinea-pig were investigated. The alpha1-adrenoceptor agonist, phenylephrine elicited concentration dependent contractile responses from preparations of epididymis. In the absence or presence of the L-type Ca2+ channel blocker, nifedipine (10 microM) the non-selective adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA, 1 microM) shifted phenylephrine concentration-response curves to the left (4 and 5 fold respectively). Following the incubation of preparations with pertussis toxin (200 ng ml(-1) 24 h) NECA shifted phenylephrine concentration-response curves to the right (5.7+/-0.9 fold). 2. In the presence of phenylephrine (1 microM), NECA and the A1 adenosine receptor selective agonists, N6-cyclopentyladenosine (CPA) and (2S)-N6-[2-endo-norbornyl]adenosine ((S)-ENBA) elicited concentration-responses dependent contractions from preparations of epididymis (pEC50 values 8.18+/-0.19, 7.79+/-0.29 and 8.15+/-0.43 respectively). The A3 adenosine receptor agonists N6-iodobenzyl-5'-N-methylcarboxamido adenosine (IBMECA) and N6-2-(4-aminophenyl) ethyladenosine (APNEA) mimicked this effect (but only at concentrations greater than 10 microM). In the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 30 nM) CPA concentration-response curves were shifted, in parallel to the right (apparent pKB 8.75+/-0.88) and the maximal response to NECA was reduced. 3. In the presence of DPCPX (100 nM) the adenosine agonist NECA and the A2A adenosine receptor selective agonist, CGS 21680 (2-p-(2-carboxyethyl)-phenethylamino-N-ethylcarboxamido adenosine), but not CPA, inhibited phenylephrine (20 microM) stimulated contractions (pIC50 7.15+/-0.48). This effect of NECA was blocked by xanthine amine congener (XAC, 1 microM) and the A2A adenosine receptor-selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-++ +ylamino]ethyl)phenol (ZM 241385; 30 nM). 4. (S)-ENBA (in the absence and presence of ZM 241385, 100 nM), but not NECA or CPA inhibited the forskolin (30 microM)-stimulated accumulation of [3H]-cyclic AMP in preparations of the epididymis of the guinea-pig (by 17+6% of control). In the presence of DPCPX (100 nM) NECA and CGS 21680, but not (S)-ENBA, increased the accumulation of [3H]-cyclic AMP in preparations of epididymis (pEC50 values 5.35+/-0.35 and 6.42+/-0.40 respectively), the NECA-induced elevation of [3H]-cyclic AMP was antagonised by XAC (apparent pKB 6.88+/-0.88) and also by the A2A adenosine receptor antagonist, ZM 241385 (apparent pKB 8.60+/-0.76). 5. These studies are consistent with the action of stable adenosine analogues at post-junctional A1 and A2 adenosine receptors in the epididymis of the guinea-pig. A1 Adenosine receptors potentiate alpha1-adrenoceptor contractility, an effect blocked by pertussis toxin, but which may not be dependent upon an inhibition of adenylyl cyclase. The epididymis of the guinea-pig also contains A2 adenosine receptors, possibly of the A2A subtype, which both inhibit contractility and also stimulate adenylyl cyclase.
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PMID:A1 and A2 adenosine receptor modulation of contractility in the cauda epididymis of the guinea-pig. 980 42

Chronic exposure of sheep adipose tissue to growth hormone (GH) in vitro decreases the ability of the adenosine analogue, N6-phenylisopropyladenosine (PIA), to inhibit isoprenaline-stimulated lipolysis by a mechanism which is dependent on both gene transcription and protein serine/threonine phosphorylation. The inhibition is not due to a change in ligand binding to the adenosine receptor, the amounts of the three isoforms of the inhibitory GTP-binding protein, Gi, or the maximum (forskolin-stimulated) adenylate cyclase activity. The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric Gi was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of Gi; GH does not appear to alter the interaction between the activated receptor and Gi. The ability of GH to alter the ability of activated Gi to inhibit adenylate cyclase activity was assessed by measuring the ability of a GTP analogue, guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG), to inhibit forskolin-stimulated adenylate cyclase activity; chronic exposure to GH prevented this effect of p[NH]ppG. Thus the attenuation of the inhibition of lipolysis by PIA by chronic exposure of adipocytes to GH appears to be due to an impairment in the interaction between adenylate cyclase and the alpha subunit of one or more isoforms of Gi.
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PMID:Regulation of the GTP-binding protein-based antilipolytic system of sheep adipocytes by growth hormone. 984 58

HEK293T cells were transiently transfected to express either the human A1 adenosine receptor together with pertussis toxin-resistant cysteine-to-glycine forms of the alpha subunits of Gi1 (C351G), Gi2 (C352G), and Gi3 (C351G) and wild-type Go1alpha or fusion proteins comprising the A1 adenosine receptor and these Gi/o G proteins to compare A1 adenosine receptor agonist-mediated activation of these Gi family G proteins upon coexpression of individual Gi/o G proteins and receptor versus expression as receptor-G protein fusion proteins. Addition of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) to membranes of pertussis toxin-treated cells resulted in a concentration-dependent stimulation of [35S]GTPgammaS binding with comparable amounts of NECA required to produce half-maximal stimulation following transfection of A1 adenosine receptor and Gi/o G proteins either as fusion proteins or as separate polypeptides. However, the magnitude of agonist-mediated activation of GTPgammaS binding was greatly enhanced by expressing the A1 adenosine receptor and Gi family G proteins from chimaeric open reading frames. This observation was consistent following the study of more than 40 agonists. No preferential activation of any G protein was observed with more than 40 A1 receptor agonists following cotransfection of receptor with G protein or transfection of receptor-G protein fusion proteins. These studies demonstrate the utility of using fusion proteins to study receptor-G protein interaction, show that the A1 adenosine receptor couples equally well to the Gi/o G proteins Gi1alpha, G i2alpha, Gi3alpha, and Go1alpha, and demonstrate that for a range of agonists there is no selectivity for activation of any particular A1 adenosine receptor-Gi/o G protein combination.
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PMID:Comparative analysis of the efficacy of A1 adenosine receptor activation of Gi/o alpha G proteins following coexpression of receptor and G protein and expression of A1 adenosine receptor-Gi/o alpha fusion proteins. 1002 19

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