Different mechanisms of action of agents acting on β‐adrenoceptors in barium‐stimulated and electrically‐stimulated rat vas deferens

Abstract

1 The relaxation induced by fl-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 (300pM). The experiments were performed in vasa of reserpine-treated rats, after blockade of a-adrenoceptors and extraneuronal uptake with dibenamine (10OpM, 30min), and neuronal uptake with cocaine (10,pM). 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 pKB values. This indicates that other mechanisms are involved besides an interaction with a single population of postsynaptic fl2-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 fl2-adrenoceptors. In addition, the antagonists produced parallel and concentrationdependent shifts of the curves of all the agonists, as expected from receptor theory. The values of pKB for a given antagonist were not modified by interchanging the agonists used, indicating a typical interaction with a single population of f2-adrenoceptors. When compared to the field-stimulated vas, the values of pKB for propranolol and IMA against isoprenaline were respectively 1.3 and 0.6 log units larger. These results suggest the fl-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 fl-adrenoceptors are mediated only by postsynaptic fl2-receptors, while other complicating factors, probably nerve-dependent presynaptic mechanisms, may be involved with electrical stimulation.

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens

“…Then, in order to verify whether the acute in vivo treatment with sibutramine in young rats is able to affect the uptake system, a mixture with neuronal and extraneuronal uptake blockers were added to the organ bath, and then a cumulative-concentrationresponse-curve for noradrenaline was constructed. Propranolol was added to the mixture to increase the available noradrenaline for α 1 -adrenoceptors or uptake system and avoid its probable action on pre or postsynaptic β-adrenoceptors (Diaz-Toledo and Jurkiewicz, 1991;Koslov and Andersson, 2013).…”