α1‐Adrenoceptors and calcium sources in adrenergic neurogenic contractions of rat vas deferens

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Abstract
1 The involvement of α1-adrenoceptor subtypes in adrenergic neurogenic contractions of different type was studied in epididymal and prostatic portions of the rat vas deferens. 2 The adrenergic component of neurogenic contractions was isolated by suramin (300 μm). Twitch-like and tonic contractions were elicited by appropriate pulse patterns of electrical field stimulation, and contractions relying on intracellular calcium mobilization and calcium entry were isolated by means of nifedipine (10 μm) and ryanodine (20 μm), respectively. Increasing concentrations of 2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), α-ethyl-3,4,5-trimethoxy-α-(3-((2-(2-methoxy-phenoxy)ethyl)-amino)-propyl)benzeneacetonitrile (HV 723), prazosin and 5-methylurapidil progressively, monophasically and with potency decreasing in that order reduced and finally abolished all types of contraction, with one exception: concentration-effect curves of 5-methylurapidil in epididymal segments in the presence of ryanodine levelled off at about 75% inhibition. In the presence of both nifedipine (10 μm) and ryanodine (20 μm), contractions were abolished. 3 Contractions elicited by exogenous noradrenaline were also studied in the presence of either nifedipine 10 μm (prostatic segments) or ryanodine 20 μm (epididymal segments). Increasing concentrations of tamsulosin, WB 4101, benoxathian, HV 723, prazosin, 5-methylurapidil and urapidil progressively, monophasically and with potency decreasing in that order reduced and eventually abolished both kinds of contraction, with two exceptions: in epididymal segments in the presence of ryanodine, the concentration-effect curve of 5-methylurapidil was biphasic and the curve of urapidil levelled off at only partial inhibition. 4 In slices prepared from the prostatic end and preincubated with [3H]-noradrenaline, WB 4101, HV 723, prazosin and 5-methylurapidil, at the highest concentrations tested against neurogenic contractions, increased only slightly the overflow of tritium elicited by trains of 50 pulses at 5 Hz. 5 It is concluded that two α1-adrenoceptor subtypes mediate adrenergic neurogenic contractions of rat vas deferens. The main one, pharmacologically α1A, activates both calcium mobilization and entry. In addition there is a second receptor, not previously detected in the vas deferens and not corresponding to any named α1 subtype, characterized by high and similar affinity for tamsulosin, WB 4101, benoxathian, HV 723 and prazosin and very low affinity for 5-methylurapidil and urapidil, and linked exclusively to calcium entry. Both subtypes and their respective transduction pathways also contribute to contractions elicited by exogenous noradrenaline. An α1B-adrenoceptor-mediated contraction was not found under any experimental conditions.