The effects of (+)- and (-)-propranolol on 3H-transmitter efflux in guinea-pig atria and the presynaptic beta-adrenoceptor hypothesis

British Journal of Pharmacology
S Kalsner

Abstract

The effects of isoprenaline and of the (+)- and (-)-isomers of propranolol on the stimulation-induced overflow of 3H-transmitter was assessed in guinea-pig atria to evaluate the hypothesis of presynaptic beta-adrenoceptors. 2 Isoprenaline (1.2 x 10(-8) M) enhanced the efflux of tritium at 2 and 5 Hz with 100 pulses and did so to a similar extent at both frequencies. 3 The (-)-isomer of propranolol (1.0 x 10(-7) M) blocked the enhancing effect of isoprenaline but did not by itself modify transmitter efflux. 4 The (+)-isomer of propranolol, almost devoid of beta-adrenoceptor blocking properties, was also effective at 1.0 x 10(-7) M in blocking the enhancement of tritium efflux by isoprenaline. 5 The (-)-isomer of propranolol (1.0 x 10(-7) M) blocked almost entirely the inotropic response to isoprenaline (3 x 10(-7) M) but even 3.0 x 10(-6) M (+)-propranolol was ineffective in antagonizing the beta-adrenoceptor-mediated contractile responses to the catecholamine. 6 It is concluded that the presynaptic site of isoprenaline action does not show the requisite stereo-specificity of beta-adrenoceptors and that a 'non-specific' action of the antagonist probably accounts for its reduction of the effect of isoprenaline.

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Citations

Aug 1, 1987·Naunyn-Schmiedeberg's Archives of Pharmacology·O A Nedergaard
Sep 30, 1983·European Journal of Pharmacology·M L SteenbergM F Lokhandwala
Jan 1, 1981·General Pharmacology·S PatelS C Verma
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Jan 1, 1990·Annals of the New York Academy of Sciences·O A Nedergaard, J Abrahamsen
Aug 30, 2008·Journal of Medicinal Chemistry·Emanuele CarosatiGabriele Cruciani

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