R. Bultmann et al., ALPHA(1)-ADRENOCEPTORS AND CALCIUM SOURCES IN ADRENERGIC NEUROGENIC CONTRACTIONS OF RAT VAS-DEFERENS, British Journal of Pharmacology, 111(1), 1994, pp. 151-158
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.