Electrical and mechanical properties of the capsular smooth muscles of the rabbit prostate in relation to the actions of the α1‐adrenoceptor blocker, YM‐12617

Open Access
Publisher Website
Google Scholar
Abstract
1 Electrical and mechanical properties of smooth muscle cells of the rabbit prostate capsule and the actions of the α1-adrenoceptor blocker, YM-12617, were investigated using microelectrode and isometric tension recording methods. 2 The capsular muscles comprised thick and thin muscle bundles. In the former, noradrenaline (NA; 0.1–10 μm) provoked the phasic and tonic mechanical responses, with twitch contractions superimposed on the tonic response. YM-12617, in concentrations over 1 nm inhibited the contraction evoked by any given concentration of NA. Yohimbine (up to 10 μm) slightly inhibited the NA-induced contraction whilst clonidine (up to 10 μm) and acetylcholine (ACh; up to 10 μm) produced no mechanical response. 3 In thin muscle bundles, NA (0.1–10 μm) produced a contraction but the phasic response was small and the tonic response was negligible. These changes were blocked by YM-12617. In contrast, ACh (0.1–10 μm) produced atropine-sensitive, large phasic and tonic responses similar to those observed on application of NA to thick muscle bundles. 4 In thin and thick muscle bundles, the mean resting membrane potentials were − 54 and − 56 mV, respectively, values which were not statistically different. However, in thick muscle bundles, NA (over 0.1 μm) depolarized the membrane in a concentration-dependent manner and produced repetitive spike generation; ACh (up to 1 μm) did not modify the membrane potential. In thin muscle bundles, the above concentrations of NA hyperpolarized the membrane but ACh produced a large depolarization with repetitive spike generation. 5 In thick muscle bundles, nifedipine (0.3 μm) blocked twitch contractions generated spontaneously or provoked by application of NA with no effect on phasic and tonic responses. The NA-induced depolarization persisted after superfusion with nifedipine up to a concentration of 1.0 μm. In a Ca-free solution containing 2 mm EGTA, NA produced only the phasic responses, and re-addition of Ca (2.6 mm) restored the generation of a tonic response. 6 After application of 0.3 μm nifedipine, the effects of YM-12617 and prazosin were observed on the tonic component of the NA-induced contraction of thick muscle bundles. The ID50 values for YM-12617 and prazosin were 1 nm and 15 nm, respectively (n = 4). YM-12617 shifted the NA concentration-response curve to the right in a concentration-dependent and parallel manner. The Schild plot yielded a straight line with slope of 0.97 ± 0.05, (n = 4). The pA2 value for YM-12617 was 10.4 ± 0.05, (n = 4). 7 In thick muscle bundles, the depolarization induced by NA (10 μm) was blocked by YM-12617 (over 1 nm) to a greater extent than by prazosin (0.1 μm). Half-inhibition of the NA (10 μm)-induced maximum depolarization by YM-12617 or prazosin occurred at concentrations of 2nm and 100 nm, respectively. 8 From these mechanical and electrical responses, the heterogeneous nature and distribution of α1-adrenoceptors and muscarinic receptors has been elucidated in capsular smooth muscles in the rabbit prostate. In both thick and thin muscle bundles, NA-induced electrical and mechanical responses were more potently inhibited by YM-12617 than by prazosin.