title: Electrical and mechanical properties of the capsular smooth muscles of the rabbit prostate in relation to the actions of the alpha 1-adrenoceptor blocker, YM-12617.
abstract: 1. Electrical and mechanical properties of smooth muscle cells of the rabbit prostate capsule and the actions of the alpha 1-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 microM) 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 microM) slightly inhibited the NA-induced contraction whilst clonidine (up to 10 microM) and acetylcholine (ACh; up to 10 microM) produced no mechanical response. 3. In thin muscle bundles, NA (0.1-10 microM) 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 microM) 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 microM) depolarized the membrane in a concentration-dependent manner and produced repetitive spike generation; ACh (up to 1 microM) 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 microM) 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 microM. 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 microM 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 thiqk muscle bundles, the depolarization induced by NA (1O microM) was blocked by YM-12617 (over 1 nM) to a greater extent than by prazosin (0.1 microM). Half-inhibition of the NA (10 microM)-induced maximum depolarization by YM-12617 or prazosin occurred at concentrations of 2 nm and 100 nM, respectively. 8. From these mechanical and electrical responses, the heterogeneous nature and distribution of alpha-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.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000109:Acetylcholine; D000317:Adrenergic alpha-Antagonists; D009543:Nifedipine; D009638:Norepinephrine; D011224:Prazosin; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; C044648:YM 12617; D000096926:Benzenesulfonamides