Article date: September 1991
By: Alejandro Diaz‐Toledo, Aron Jurkiewicz, in Volume 104, Issue 1, pages 277-283
The relaxation induced by β‐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 μm). The experiments were performed in vasa of reserpine‐treated rats, after blockade of α‐adrenoceptors and extraneuronal uptake with dibenamine (10 μm, 30 min), and neuronal uptake with cocaine (10 μm).
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 β2‐adrenoceptors (Iso > Ad ≫ NA).
When twitch responses were used, the non‐selective β‐antagonist, propranolol, caused a concentration‐dependent parallel shift to the right of Iso concentration‐response curves. Similar shifts were obtained by use of the β2‐antagonist, isopropylmethoxamine (IMA), and higher doses of the β1‐antagonist, practolol, according to the expectations from receptor occupation theory. Practolol presented the lowest value of pKB, 5.03, corroborating the presence of β2‐adrenoceptors.
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 β2‐adrenoceptors.
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 β2‐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 pKB for a given antagonist were not modified by interchanging the agonists used, indicating a typical interaction with a single population of β2‐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 β‐adrenoceptor agents act by different mechanisms of action in barium‐stimulated and electrically‐stimulated vas.
It is suggested that when barium is used, the effects of agents acting on β‐adrenoceptors are mediated only by postsynaptic β2‐receptors, while other complicating factors, probably nerve‐dependent presynaptic mechanisms, may be involved with electrical stimulation.
The relaxation induced by β‐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 μm). The experiments were performed in vasa of reserpine‐treated rats, after blockade of α‐adrenoceptors and extraneuronal uptake with dibenamine (10 μm, 30 min), and neuronal uptake with cocaine (10 μm).
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 β2‐adrenoceptors (Iso > Ad ≫ NA).
When twitch responses were used, the non‐selective β‐antagonist, propranolol, caused a concentration‐dependent parallel shift to the right of Iso concentration‐response curves. Similar shifts were obtained by use of the β2‐antagonist, isopropylmethoxamine (IMA), and higher doses of the β1‐antagonist, practolol, according to the expectations from receptor occupation theory. Practolol presented the lowest value of pKB, 5.03, corroborating the presence of β2‐adrenoceptors.
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 β2‐adrenoceptors.
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 β2‐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 pKB for a given antagonist were not modified by interchanging the agonists used, indicating a typical interaction with a single population of β2‐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 β‐adrenoceptor agents act by different mechanisms of action in barium‐stimulated and electrically‐stimulated vas.
It is suggested that when barium is used, the effects of agents acting on β‐adrenoceptors are mediated only by postsynaptic β2‐receptors, while other complicating factors, probably nerve‐dependent presynaptic mechanisms, may be involved with electrical stimulation.
DOI: 10.1111/j.1476-5381.1991.tb12419.x
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