Adrenoceptor and Cholinoceptor Mediated Responses of the Isolated Human Urethra

Abstract

Smooth muscle preparations from various parts of the isolated urethra and the urethrovesical junction were obtained from male and female patients undergoing total cysto-urethrectomy because of bladder malignancy. The preparations were suspended in Krebs solution (37°C) bubbled with carbogen. Isometric tension was recorded. Twenty-nine out of 42 drug-responsive preparations exhibited a spontaneous contractile activity. This was unaffected by tetrodotoxin, atropine, and phenoxybenzamine, suggesting it was of myogenic origin. Noradrenalin contracted preparations from all parts of the urethra, including the urethrovesical junction, in a concentration-related way. No differences in the sensitivity to noradrenalin between different parts of the male or female urethra could be established. The noradrenalin-induced effects were inhibited by phenoxybenzamine, suggesting that they were mediated via α-adrenoceptors. Adrenalin, phenylephrine, ephedrine, and norephedrine had contracting effects that could be blocked by phenoxybenzamine. The contractions produced by ephedrine and norephedrine developed slower than those caused by noradrenalin, adrenalin, and phenylephrine. Isoprenaline and terbutaline inhibited spontaneous activity, and relaxed preparations contracted by noradrenalin. The effects were inhibited by propranolol, suggesting that they were mediated via β-adrenoceptors. Preparations from all parts of the urethra distal to the urethrovesical junction exhibited a low sensitivity to acetylcholine. Acetylcholine in concentrations up to 20 μg/ml produced no effect or only a weak contraction. Preparations from the urethrovesical junction had a varying sensitivity to acetylcholine, but were contracted by the drug. The contracting effects of acetylcholine were blocked by atropine, suggesting that they were mediated via muscarinic cholinoceptors.