Adrenoceptor and cholinoceptor mediated effects in the isolated urethra of cat and guinea-pig.

1. Preparations of isolated bladder-urethral junction from cats and guinea-pigs were suspended in Krebs solution (37 degrees C) which was bubbled with carbogen. The urethral lumen was perfused at a very low rate (1-3 ml/h) with Krebs solution. Resistance to flow and changes in longitudinal tension (initial setting 0-5 g) were recorded. In additional experiments, tension changes in urethral circular muscle preparations were registered. 2. The urethral preparations had a basal resistance to flow within the range 5-20 cm H2O. They had a spontaneous contractile activity that was unaffected by atropine 0-1 mug/ml, phenoxybenzamine 0-1 mug/ml, and tetrodotoxin 0-1-0-5 mug/ml, suggesting it was of myogenic origin. 3. The basal characteristics and the drug-induced changes in the perfused urethras were independent of whether the longitudinal tension was recorded isometrically or isotonically, or whether the perfusion was made retrograde or antegrade. Passive changes in longitudinal tension between 0-5 and 2-0 g did not affect the resistance to flow through the urethra. 4. Adrenaline and noradrenaline, 0-01-1 mug/ml, increased longitudinal tension and resistance to flow in the perfused preparations. The effects, which were sustained and concentration-related, were blocked or reversed into inhibition in the presence of phenoxybenzamine, 0-1 mug/ml. This finding suggests that the stimulatory effects were mediated via alpha-receptors. 5. Isoprenaline, 0-001-0-005 mug/ml, relaxed and inhibited the activity in the cat urethral smooth muscle and decreased the resistance to flow both under basal conditions and when the urethra was contracted by noradrenaline or acetylcholine. The inhibitory effects were blocked by propranolol, 0-1 mug/ml, suggesting that they were mediated via beta-receptors. In guinea-pig preparations, no effect of isoprenaline was observed. 6. Acetylcholine, 0-02-0-5 mug/ml, increased the longitudinal tension and the resistance to flow through the urethras. The latter effect was less pronounced than that produced by noradrenaline, especially in the guinea-pig preparations. Noradrenaline was also more effective than ecetylcholine in contracting the circular muscle of the urethra. The effect of acetylcholine was blocked by atropine, 0-1 mug/ml, suggesting that the contractions were mediated through muscarinic cholinoceptors.