UMLS:C0043167 - FACTA Search

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)

We have previously shown that adenosine, acting at an A1 receptor, contracts the smooth muscle of virgin guinea pig uterus (M. A. Smith, I. L. O. Buxton, and D. P. Westfall. J. Pharmacol, Exp. Ther. 247: 1059-1063, 1988) and is not coupled to the expected inhibition of adenylate cyclase (M. A. Smith, J. L. Silverstein, D. P. Westfall, and I. L. O. Buxton. Cell. Signal. 1: 357-365, 1989). To probe the importance of contractile actions of adenosine in uterine smooth muscle and to further characterize the signal transduction pathway involved in A1-receptor action, we have studied the adenosine receptor and its coupling in pregnant guinea pig myometrium. Adenosine agonist and antagonist radioligands bind to saturable sites of the A1 subtype homogeneously distributed in the smooth muscle of pregnant guinea pig uterus. Agonist competition of antagonist radioligand binding in both the absence and presence of guanine nucleotide reveals high and low agonist affinity states of the receptor. Pretreatment of tissues with pertussis toxin (PTx) shifts the high-affinity sites to a lower affinity but does not affect low-affinity sites, whereas agonist competition in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) is indistinguishable from the control, which is consistent with coupling of A1 receptors to both PTx-sensitive and PTx-insensitive GTP-binding proteins. Adenosine receptor inhibition of adenylate cyclase activity is prevented after pretreatment of the tissue with PTx, whereas increased inositol phosphate production is not. The data presented here are consistent with coupling of the A1 receptor to dual effectors in the pregnant state of the smooth muscle. The unique action of an A1 receptor to contract mammalian smooth muscle and the appearance, only in the pregnant state, of coupling to adenylate cyclase inhibition suggest a role for adenosine in parturition biology.
...
PMID:Smooth muscle adenosine A1 receptors couple to disparate effectors by distinct G proteins in pregnant myometrium. 190 2

The effects of adenosine receptor stimulation on the contractile force of rabbit isolated left atrial preparations in the absence and presence of cAMP-generating and cAMP-independent agonists were investigated. Adenosine and the stable adenosine analogues 5'-(N-ethyl)carboxamido adenosine (NECA) and (-)-N6-phenylisopropyladenosine (R-PIA) produced a concentration-dependent direct negative inotropic effect. Responses to NECA and R-PIA were insensitive to atropine and were shifted to the right by the adenosine receptor antagonist 3-isobutyl-1-methyl xanthine (IBMX). NECA and R-PIA were found to reverse positive inotropic responses of left atria to the beta-adrenoceptor agonist, isoproterenol, but were less effective at reversing positive inotropic responses to the adenylate cyclase activator, forskolin, and were almost ineffective at reversing positive inotropic responses to alpha-adrenoceptor stimulation. Neither NECA nor R-PIA had a significant effect on basal cAMP levels or on cAMP levels elevated by isoproterenol in rabbit left atria. Similarly, R-PIA had no significant effect on basal cAMP levels or isoproterenol-induced increases in cAMP in the presence of adenosine deaminase to remove the influence of endogenous adenosine. Pretreatment of rabbits with 1.75 micrograms/kg pertussis toxin attenuated both the direct negative inotropic response of left atria to NECA and responses to NECA in the presence of isoproterenol and forskolin to a similar extent. Pretreatment of left atrial preparations with the potassium channel antagonist 4-aminopyridine resulted in a dose dependent attenuation of responses to NECA alone and in the presence of isoproterenol and forskolin. These data suggest that adenosine receptors in rabbit left atria are not coupled to adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The interaction of adenosine analogues with cAMP-generating and cAMP-independent positive inotropic agents in rabbit left atrium. 196 30

Adenosine A1 receptors have been described in coated vesicles isolated from bovine brain (Gonzalez-Calero et al., J. Neurochem. 1990, 55, 106-113). Addition of non hydrolyzable GTP analogue (guanyl-5-yl-imidodiphosphate) caused a transition of the receptor from the high- to the low-affinity state, without any significant change in the total binding sites. The presence of G-proteins has been investigated by pertussis and cholera toxins catalyzed ADP-ribosylation. A band of Mr = 41,000 D, similar to the alpha Gi subunit, was specifically labeled in the presence of preactivated pertussis toxin. Bands of Mr = 42,000 D and Mr = 47,000 D were specifically labeled in the presence of preactivated cholera toxin. These results confirm the presence of GTP binding proteins (alpha Gi and alpha Gs) in coated vesicles isolated from bovine brain.
...
PMID:Coupling of adenosine A1 receptors to a G-protein in coated vesicles isolated from bovine brain: presence of pertussis and cholera toxin substrates. 197 3

1. In intact ventricular preparation, adenosine has been shown to reduce the beta-adrenoceptor-induced increase in contraction (the anti-adrenergic effect). In the present study we have investigated this effect of adenosine on isolated ventricular myocytes from failing human heart and normal guinea-pig and rat heart. 2. Adenosine in the absence of beta-adrenoceptor-mediated stimulation had no effect on contraction in human and guinea-pig myocytes but produced a variable effect in rat myocytes. 3. 8-Cyclopentyl 1,3-dipropylxanthine (CPX), a selective A1-receptor antagonist, antagonised the anti-adrenergic effect of adenosine in guinea-pig myocytes. 4. The anti-adrenergic effect of adenosine was greater in guinea-pig than rat myocytes and even more pronounced in cells isolated from failing human heart. 5. Pertussis toxin-pretreatment at 35 degrees C of guinea-pig and human myocytes abolished the anti-adrenergic effect of adenosine. Longer exposure to higher concentrations of pertussis toxin was required for complete abolition in human compared to guinea-pig cells. 6. These results support the suggestion that the adenosine receptors mediating the anti-adrenergic effect of adenosine are of the A1 subtype and are coupled to the inhibitory guanine nucleotide binding protein, Gi/Go. 7. Pertussis toxin pretreatment increased the sensitivity of guinea-pig myocytes to isoprenaline in the absence of adenosine; the EC50 value was decreased by a factor of 10. This suggests that Gi may exert a tonic inhibitory effect on the beta-adrenoceptor/adenylate cyclase interaction in normal myocardium.
...
PMID:The anti-adrenergic effect of adenosine and its blockade by pertussis toxin: a comparative study in myocytes isolated from guinea-pig, rat and failing human hearts. 197 12

We studied the effect of adenosine on Na+/Ca2+ exchange activity in ewe heart ventricular sarcolemmal vesicles. Adenosine was found to stimulate Na+/Ca2+ exchange activity in a dose-dependent manner from 0.1 nM to 10 microM, with maximal stimulation (40%) at 0.1 microM adenosine. The Vmax of Na+/Ca2+ exchange was increased, but the Km for Ca2+ was not altered. The effect of adenosine was specific since 1 microM adenine, inosine, and guanosine led to less than 15% stimulation, and adenosine diphosphate had no effect. Caffeine antagonized the activation of Na+/Ca2+ exchange by adenosine, and the order of potency of adenosine analogs was N6-(L-2-phenylisopropyl)adenosine = N6-cyclohexyladenosine = 5'-(N- ethylcarboxamido)adenosine much greater than N6-(D-2-phenylisopropyl)adenosine, indicating the involvement of A1 subclass receptors. The effect of adenosine was mimicked by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and blocked by pertussis toxin treatment. Taken together, these results suggest that A1 subclass receptors coupled to a pertussis toxin-sensitive G protein mediate the activation of Na+/Ca2+ exchange activity by adenosine. We conclude that the negative inotropic effect of adenosine in ventricular muscle, antagonistic toward cyclic AMP, may involve activation of Na+/Ca2+ exchange.
...
PMID:Activation of Na+/Ca2+ exchange by adenosine in ewe heart sarcolemma is mediated by a pertussis toxin-sensitive G protein. 212 Feb 8

The effects of adenosine (A) and the nonmetabolizable adenosine analogs, N-ethylcarboxamidoadenosine (NECA), L-phenylisopropyladenosine (L-PIA), D-PIA and 2-chloroadenosine (2CHA) were examined on the IgE-dependent mediator release from RBL-2H3 cells, a model for mast-cell function. Adenosine and the adenosine analogs failed to influence mediator release from cells, previously sensitized with monoclonal anti-TNP mouse immunoglobulin E (anti-TNP IgE), when added alone. When added prior to conjugated trinitrophenol-ovalbumin (TNP-OVA), adenosine and the adenosine analogs (10(-8)-10(-4) M) significantly potentiated the release of both histamine (marker for degranulation) and peptidoleukotrienes (LT) (marker for de novo synthesized mediators). The effects were concentration-dependent with the potency order being L-PIA greater than NECA greater than A greater than D-PIA, 2CHA. The stimulatory effect on both histamine and LT release were reversed by prior treatment of the cells with pertussis toxin but not by the purinoceptor antagonists, theophylline and 8-phenyltheophylline, nor adenosine uptake blockers. At higher concentrations (above 10(-5) M), adenosine and adenosine analogs were also inhibitory on LT but not on histamine release. This inhibition was more evident on pertussis-toxin-treated cells in which there was no effect of adenosine or adenosine analogs on histamine release, but a concentration-dependent inhibition of IgE-dependent LT release. These findings demonstrate that adenosine analogs have two distinct mechanisms on mediator release from RBL-2H3 cells; a stimulatory effect on both histamine and LT release, mediated via a pertussis-toxin-sensitive G protein and an inhibitory effect on LT release via a pertussis-toxin-insensitive pathway. An abstract of this work has been published.
...
PMID:Pertussis toxin pretreatment reveals differential effects of adenosine analogs on IgE-dependent histamine and peptidoleukotriene release from RBL-2H3 cells. 216 18

Human rTNF-alpha (greater than or equal to U/ml) decreased PMN nondirected and directed migration to FMLP to approximately 50% of control. Adenosine (100 microM) almost completely restored hrTNF-inhibited migration (nondirected from 54 to 92% and directed migration to from 54 to 93% of control). The lowest concentration of adenosine that restored hrTNF-inhibited migration was 3 microM, and the adenosine analogue, 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA) was more potent than adenosine. Although CPCA binds to A2-receptors and stimulates adenylate cyclase, the reversal of hrTNF-inhibited chemotaxis was found to be independent of both PMN cAMP content and binding to A2-receptors, because neither 8-Br-cAMP nor pertussis adenylate cyclase restored hrTNF-inhibited PMN chemotaxis and the A2-receptor antagonist, 1,3-dipropyl-7-methylxanthine decreased CPCA stimulated cAMP but enhanced CPCA-restoration of hrTNF-inhibited chemotaxis. The effect of adenosine could be augmented by inhibition of adenosine uptake and decreased by adenosine deamination. Pentoxifylline, (3,7 dimethyl-1-[5 oxo-hexyl] xanthine), like adenosine also restored PMN chemotaxis inhibited by hrTNF. The adenosine receptor antagonist, 1,3-dipropyl-8(phenyl-p-acrylate)-xanthine (BW A1433U), decreased restoration of hrTNF-inhibited chemotaxis by CPCA or pentoxifylline. Thus, the inhibitory effect of hrTNF on PMN migration can be counteracted by adenosine, CPCA, pentoxifylline, and compounds that increase adenosine availability to the surface of the PMN. Inasmuch as an A1-selective agonist N6-cyclopentyladenosine was less active, and the action of the A2-selective agonist CPCA was enhanced by an A2-receptor antagonist, we hypothesize that neither A1 or A2 receptors are involved in adenosine restoration of hrTNF-inhibited chemotaxis. Further, increased cAMP, an A2-regulated event, does not cause the effect, and adenosine restoration of hrTNF-inhibited migration does not appear to be mediated by changes in PMN [F-actin], FMLP receptor expression, or cytosolic calcium. Hence, the restoration of hrTNF-inhibited chemotaxis is controlled by a novel cyclic AMP-independent action on the PMN surface.
...
PMID:Adenosine and related compounds counteract tumor necrosis factor-alpha inhibition of neutrophil migration: implication of a novel cyclic AMP-independent action on the cell surface. 216 64

Adenosine, an endogenously released purine, modulates the functions of many cells through surface A1 and A2 receptors. We examined the hypothesis that adenosine receptor ligation regulates Fc gamma R-triggered inflammatory response by polymorphonuclear leukocytes (PMN), a response which is critical to the pathogenesis of immune complex diseases. The effects of adenosine analogs on Fc gamma R-mediated phagocytosis and superoxide anion (O2-) generation in human neutrophils were investigated. 5'(N-ethyl)carboxamidoadenosine (NECA), the most potent A2 receptor agonist, inhibited Fc gamma R-mediated phagocytosis and O2- generation, whereas N6-cyclopentyladenosine (CPA), a highly selective A1 receptor agonist, enhanced these functions. The effects of the adenosine analogs were markedly accentuated in neutrophils adherent to biologic surfaces. Both the inhibition by NECA and the enhancement by CPA of PMN Fc gamma R functions were blocked by the adenosine receptor antagonist 8-p-sulfophenyltheophylline, which suggests that occupancy of surface adenosine receptors mediated the actions of these analogs. Because A1 receptors on PMN are linked to pertussis toxin-sensitive G proteins, our evidence that pertussis toxin blocked the effects on Fc gamma R function brought about by CPA but not by NECA further supports the hypothesis that CPA acts via an A1 receptor. Our data indicate that adenosine A1 and A2 receptors modulate neutrophil Fc gamma R function in opposing ways, allowing for a concentration-dependent, adenosine-regulated feed-back loop. At low concentrations there is enhancement of neutrophil Fc gamma R function via PMN A1 receptors, whereas at higher concentrations (those which may occur at sites of damaged tissues), there is inhibition via A2 receptors. Our observation that adenosine analogs had more potent effects on adherent neutrophils emphasizes the potential importance of adenosine as a modulator of Fc gamma R-triggered inflammation in vivo.
...
PMID:Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory. 216 19

(Rp)-Adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) is a highly specific antagonist of the cAMP-dependent protein kinase from eukaryotic cells and is a very poor substrate for phosphodiesterases. It is therefore a useful tool for investigating the role of cAMP as a second messenger in a variety of biological systems. Taking advantage of stereospecific inversion of configuration around the alpha-phosphate during the adenylate cyclase reaction, we have developed a method for the preparative enzymatic synthesis of the Rp diastereomer of adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) from the Sp diastereomer of adenosine 5'-O-(1-thiotriphosphate) ((Sp)-ATP alpha S). The adenylate cyclase from Bordetella pertussis, partially purified by calmodulin affinity chromatography, cyclizes (Sp)-ATP alpha S approximately 40-fold more slowly than ATP, but binds (Sp)-ATP alpha S with about 10-fold higher affinity than ATP. The triethylammonium salt of the reaction product can be purified by elution from a gravity flow reversed-phase C18 column with a linear gradient of increasing concentrations of methanol. Yields of the pure (Rp)-cAMPS product of a synthesis with 2 mg of substrate are about 75%.
...
PMID:Enzymatic synthesis of the cAMP antagonist (Rp)-adenosine 3',5'-monophosphorothioate on a preparative scale. 217 77

Adenosine receptors in the smooth muscle cell line DDT1 MF-2 were studied by radioligand binding using the A1 receptor-selective antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine [( 3H]DPCPX) as the ligand. Binding characteristics were similar in intact cells and in membranes (KD value of approximately 1 nM). The maximum binding amounted to 183 fmol/10(6) intact cells or 344 fmol/mg of membranes. To characterize the receptor, competition experiments were performed by inhibiting [3H]DPCPX binding with several adenosine agonists and antagonists. Adenosine receptor antagonists appeared to bind to a single class of binding site, both in membranes and intact cells. The order of potency was DPCPX = CGS 15943A greater than 8-cyclopentyl-1,3-dimethylxanthine greater than 8-(p-sulfophenyl)-theophylline greater than 3-isobutyl-1-methylxanthine greater than theophylline. Competition curves with adenosine agonists in membranes were best described by a two-site rather than a one-site model. At equilibrium in intact cells, only a single site was detected at both 4 degrees and 25 degrees. However, short term incubations (1-4 min) at 25 degrees showed biphasic binding curves in intact cells. The equilibrium KD values for intact cells were similar to the low affinity KD values in membranes (KL). The order of potency was N6-cyclopentyladenosine greater than or equal to (-)-(R)-N6-phenylisopropyladenosine[(R)-PIA] greater than or equal to N6-cyclohexyl adenosine greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than 2-chloroadenosine greater than adenosine (intact cells only) greater than 2-phenylaminoadenosine (CV 1808). Treatment of cells with pertussis toxin ADP-ribosylated GTP-binding proteins and eliminated the high affinity agonist binding in membranes but did not affect binding to intact cells. The addition of GTP (100 microM) also shifted the competition curves from bi- to monophasic curves in membranes. Adenosine receptor agonists inhibited the formation of cAMP induced by isoprenaline (IC50 for (R)-PIA, 0.4 nM). This inhibition could be prevented with adenosine receptor antagonists. Pretreatment with pertussis toxin also reversed these effects and actually revealed functional A2 receptors, as shown by the formation of cAMP induced by NECA. In conclusion, the equilibrium binding of A1 receptor agonists to intact smooth muscle cells is similar to the low affinity binding observed in membranes. In addition, it is suggested that agonists may transiently convert the A1 receptor from a "resting" low affinity state to a high affinity state coupled to a GTP-binding protein.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Characterization of adenosine A1 receptors in intact DDT1 MF-2 smooth muscle cells. 217 73

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>