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  • 1
    ISSN: 1432-1912
    Keywords: Rat vas deferens ; Guinea-pig taenia coli ; P2-purinoceptor antagonists ; P2X-purinoceptor ; P2Y-purinoceptor ; Ecto-nucleotidases ; Isothiocyanates ; DIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of eight small aromatic isothiocyanatosulphonates, of the aliphatic 2-isothiocyanatoethene-1-sulphonate (IES), and of the parent amines were studied on contractions of the rat vas deferens elicited by α,β-methy-lene ATP (α,β-MeATP; mediated by P2X-purinoceptors), relaxations of the carbachol-precontracted guinea-pig taenia coli elicited by adenosine 5′-O-(2-thiodiphosphate) (ADPβS; mediated by P2Y-purinoceptors), and the degradation of ATP by rat vas deferens tissue. The aromatic isothiocyanato-sulphonates all reduced contractions of the rat vas deferens elicited by α,β-methy-lene ATP. The antagonism was non-competitive, with depression of the maximum of the concentration-response curve of α,β-MeATP and incomplete reversibility. The IC50 values were between 11 and 54 μM. In the guineapig taenia coli, the aromatic compounds shifted the concentration-response curve of ADPβS to the right in a surmountable manner (one exception), and where three concentrations were tested, the Arunlakshana-Schild regression was linear and its slope did not differ from 1. The apparent K d values were between 10 and 214 μM. The removal of ATP from the medium by vas deferens tissue was decreased by the aromatic isothiocyanates with IC25% values between 25 and 464 μM. IES and the parent amines were inactive or almost inactive (parent amines not tested on ATP breakdown). The results indicate that the isothiocyanato residue as well as the aromatic core are essential for P2-purinoceptor blockade. At the P2X-purinoceptor, potency increases with the size of the molecules but is independent of the position of the isothiocyanato and sulphonate substituents. No simple structure-activity relationship for the P2Y-purinoceptor and the ATP-degrading ecto-nucleotidases can be derived beyond the apparent lack of a major influence of the position of the substituents. 2-Isothiocyanatonaphthalene1-sulphonate (β-INS) seems to be interesting because of relatively high P2X-selectivity versus both the P2Y-purinoceptor and ecto-nucleotidases.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 347 (1993), S. 527-533 
    ISSN: 1432-1912
    Keywords: Rat vas deferens ; Ethanol ; P2X-purino-ceptors ; Purinergic transmission ; Adrenergic transmission ; Ligand-gated ion channels ; L-type Ca2+ channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Some ligand-gated ion channels are important sites of action of ethanol. The aim of the study was to find out whether the P2X-purinoceptors mediating contraction of the rat isolated vas deferens also are selectively sensitive to ethanol. Contractions were elicited by ATP (1 mmol/1), α,ß-methylene ATP (0.3 μmol/1), noradrenaline (3 μmol/1), high K+ (20 mmol/1) or electrical (neural) stimulation by pairs of pulses 3 s apart. In electrical stimulation experiments, purinergic and adrenergic response components were isolated by prazosin and suramin, respectively. Concentration-effect curves were determined for ethanol and, for comparison, nifedipine. Tritium outflow from tissues preincubated with 3H-noradrenaline was also examined. Ethanol at relatively low concentrations reduced contractions elicited by high K+ (IC30 145 mmol/1), ATP (IC30 211 mmol/1) and α,ß-methylene ATP(IC30 215 mmol/1) as well the purinergic component of neurogenic twitches (IC30 110-126 mmol/1; a significant effect at 10–32 mmol/1) and the adrenergic component of twitch 2 of the twitch pairs (IC30 63 mmol/1). These contractions also were very sensitive to nifedipine. Higher concentrations of ethanol were needed to reduce contractions elicited by noradrenaline (IC30 365 mmol/1) and the adrenergic component of twitch 1 of the twitch pairs (IC30 382 mmol/1), contractions that also were less sensitive to nifedipine. Ethanol 1 mol/l abolished all contractions. In contrast, concentration-effect curves for the inhibition by nifedipine of contractions evoked by ATP, α,ß-methylene ATP and noradrenaline (rapid phase) levelled off at 60–70% inhibition. The contractions that remained when these agonists were administered in the presence of nifedipine 10 μmol/l were depressed by ethanol (IC30 242–387 mmol/1). Ethanol 320 mmol/1 did not change the electrically evoked overflow of tritium from vasa deferentia preincubated with 3H-noradrenaline. It is concluded that the P2X-purinoceptors of rat vas deferens smooth muscle, although ligand-gated ion channels, are not selectively sensitive to ethanol. The reduction of contractions can be explained by, first, an inhibition of L-type voltage-dependent Ca2+ channels for which relatively low concentrations of ethanol are needed, and second, a “non-specific” depressant effect at an unknown site or at unknown sites which requires relatively high concentrations.
    Type of Medium: Electronic Resource
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