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Opposite modulation of noradrenaline and ATP release in guinea-pig vas deferens through prejunctional β-adrenoceptors: evidence for the β2 subtype

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Abstract

Activation of prejunctional β-adrenoceptors has been suggested to increase the release of noradrenaline but to decrease the neural release of ATP in the guinea-pig vas deferens. Experiments were carried out to determine the subtype of β-adrenoceptor involved.

In [3H]-noradrenaline-preincubated tissues superfused with medium containing prazosin and suramin, isoprenaline (1–100 nM), salbutamol (0.01–1 μM) and terbutaline (0.1–10 μM) increased the overflow of tritium but reduced the overflow of ATP elicited by electrical stimulation (210 pulses/7 Hz). The effects of isoprenaline were blocked by the β2-selective antagonist 1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551; 100 nM). In prazosin- and suramin-free medium, isoprenaline (100 nM) did not change the overflow of ATP elicited by exogenous noradrenaline (10 μM). Isoprenaline (1–100 nM), salbutamol (0.01–1 μM) and terbutaline (0.1–10 μM) reduced the initial twitch contraction elicited by electrical stimulation (210 pulses/7 Hz) in prazosin-and suramin-free medium as well as the isolated purinergic neurogenic contraction obtained by exposure to prazosin. They increased or tended to increase the secondary sustained contraction elicited by electrical stimulation in prazosin- and suramin-free medium as well as the isolated adrenergic neurogenic contraction obtained in the presence of suramin. The inhibition by isoprenaline of the isolated purinergic contraction was attenuated by ICI 118,551 (100 nM) but not by the β1-selective antagonist 1-[2-((3carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol (CGP 20712A; 100 nM).

The results confirm the opposite β-adrenoceptor-mediated modulation of noradrenaline and neural ATP release in the guinea-pig vas deferens. They show that the prejunctional β-adrenoceptor is of the β2 subtype.

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Driessen, B., Bültmann, R., Gonçalves, J. et al. Opposite modulation of noradrenaline and ATP release in guinea-pig vas deferens through prejunctional β-adrenoceptors: evidence for the β2 subtype. Naunyn-Schmiedeberg's Arch Pharmacol 353, 564–571 (1996). https://doi.org/10.1007/BF00169177

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  • DOI: https://doi.org/10.1007/BF00169177

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