ALPHA(1)-ADRENOCEPTORS AND CALCIUM SOURCES IN ADRENERGIC NEUROGENIC CONTRACTIONS OF RAT VAS-DEFERENS

1 The involvement of alpha(1)-adrenoceptor subtypes in adrenergic neur ogenic contractions of different type was studied in epididymal and pr ostatic portions of the rat vas deferens. 2 The adrenergic component o f neurogenic contractions was isolated by suramin (300 mu M). Twitch-l ike and tonic contractions were elicited by appropriate pulse patterns of electrical field stimulation, and contractions relying on intracel lular calcium mobilization and calcium entry were isolated by means of nifedipine (10 mu M) and ryanodine (20 mu M), respectively. Increasin g concentrations of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4-benz odioxane (WB 4101), alpha-ethyl-3,4,5-trimethoxy-alpha-(3-( (2-methoxy phenoxy)ethyl)-amino)-propyl)benzeneacet (HV723), prazosin and 5-methy lurapidil progressively, monophasically and with potency decreasing in that order reduced and finally abolished all types of contraction, wi th one exception: concentration-effect curves of 5-methylurapidil in e pididymal segments in the presence of ryanodine levelled off at about 75% inhibition. In the presence of both nifedipine (10 mu M) and ryano dine (20 mu M), contractions were abolished. 3 Contractions elicited b y exogenous noradrenaline were also studied in the presence of either nifedipine 10 mu M (prostatic segments) or ryanodine 20 mu M (epididym al segments). Increasing concentrations of tamsulosin, WB 4101, benoxa thian, HV 723, prazosin, 5-methylurapidil and urapidil progressively, monophasically and with potency decreasing in that order reduced and e ventually abolished both kinds of contraction, with two exceptions: in epididymal segments in the presence of ryanodine, the concentration-e ffect curve of 5-methylurapidil was biphasic and the curve of urapidil levelled off at only partial inhibition. 4 In slices prepared from th e prostatic end and preincubated with [H-3]-noradrenaline, WB4101, HV 723, prazosin and 5-methylurapidil, at the highest concentrations test ed against neurogenic contractions, increased only slightly the overfl ow of tritium elicited by trains of 50 pulses at 5 Hz. 5 It is conclud ed that two alpha(1)-adrenoceptor subtypes mediate adrenergic neurogen ic contractions of rat vas deferens. The main one, pharmacologically a lpha(1A), activates both calcium mobilization and entry. In addition t here is a second receptor, not previously detected in the vas deferens and not corresponding to any named alpha(1) subtype, characterized by high and similar affinity for tamsulosin, WB 4101, benoxathian, HV 72 3 and prazosin and very low affinity for 5-methylurapidil and urapidil , and linked exclusively to calcium entry. Both subtypes and their res pective transduction pathways also contribute to contractions elicited by exogenous noradrenaline. An alpha(1B)-adrenoceptor-mediated contra ction was not found under any experimental conditions.