| dc.description.abstract | 1 The relaxation induced by beta-adrenoceptor agonists in rat vas deferens was examined under two different experimental conditions: on electrically-induced twitch responses (35 V, 3 ms, 0.07 Hz), and on contractions induced by single doses of barium chloride (300-mu-M). The experiments were performed in vasa of reserpine-treated rats, after blockade of alpha-adrenoceptors and extraneuronal uptake with dibenamine (10-mu-M, 30 min), and neuronal uptake with cocaine (10-mu-M).2 When twitch responses were used, the values of pD2, interpolated from cumulative concentration-response curves for isoprenaline (Iso), adrenaline (Ad), and noradrenaline (NA) showed a rank order of potency consistent with the presence of beta-2-adrenoceptors (Iso > Ad >> NA).3 When twitch responses were used, the non-selective beta-antagonist, propranolol, caused a concentration-dependent parallel shift to the right of Iso concentration-response curves. Similar shifts were obtained by use of the beta-2-antagonist, isopropylmethoxamine (IMA), and higher doses of the beta-1-antagonist, practolol, according to the expectations from receptor occupation theory. Practolol presented the lowest value of pK(B), 5.03, corroborating the presence of beta-2-adrenoceptors.4 When twitch responses were used, and Ad or NA employed instead of Iso, the antagonists produced shifts of concentration-response curves which were smaller than expected from theory, precluding the determination of pK(B) values. This indicates that other mechanisms are involved besides an interaction with a single population of postsynaptic beta-2-adrenoceptors.5 When barium chloride was used instead of twitch responses, although the potencies of Iso and Ad were increased respectively by about 30 fold and 5 fold, the rank order of potency was still consistent with an interaction with beta-2-adrenoceptors. In addition, the antagonists produced parallel and concentration-dependent shifts of the curves of all the agonists, as expected from receptor theory. The values of pK(B) for a given antagonist were not modified by interchanging the agonists used, indicating a typical interaction with a single population of beta-2-adrenoceptors. When compared to the field-stimulated vas, the values of pK(B) for propranolol and IMA against isoprenaline were respectively 1.3 and 0.6 log units larger. These results suggest the beta-adrenoceptor agents act by different mechanisms of action in barium-stimulated and electrically-stimulated vas.6 It is suggested that when barium is used, the effects of agents acting on beta-adrenoceptors are mediated only by postsynaptic beta-2-receptors, while other complicating factors, probably nerve-dependent presynaptic mechanisms, may be involved with electrical stimulation. | |
