Noradrenaline In Smooth Muscle Research Articles

Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy.

1 The effects of some sympathomimetic amines and of carbachol and potassium chloride upon the contractility of epididymal halves of the rat vas deferens have been examined in vitro at several times following vasectomy by medial transection of the vas deferens in vivo. The inhibitory effects of noradrenaline and the excitatory effects of potassium chloride upon prostatic halves of transected tissues were also studied. 2 Partially denervated epididymal segments, taken 2 days after surgery, were spontaneously active, and responses to KCl (80 mmol/l) and maximum responses to phenylephrine were enhanced. These effects were not observed with preparations taken at later times. Spontaneous activity and enhancement of responses to KCl were abolished by guanethidine (0.1 mumol/l). 3 Supersensitivity to noradrenaline was observed in fully denervated epididymal halves of vasa deferentia taken 7-183 days after transection. The supersensitivity consisted of a leftward shift in the log concentration-response curves for noradrenaline constructed upon operated, relative to those obtained upon unoperated preparations. Supersensitivity to phenylephrine but not to methoxamine or to carbachol was also evident. 4 The magnitude of the leftward shift in the log concentration-response curve for noradrenaline in operated epididymal segments approached that produced, in unoperated segments, by nisoxetine (0.1 mumol/l). This inhibitor of neuronal uptake did not enhance the potency of noradrenaline in operated segments. 5 Prazosin (50 nmol/l) antagonized the effect of phenylephrine upon both operated and unoperated epididymal segments. The antagonism was significantly greater upon operated segments than upon unoperated segments 4 and 28 days after surgery. 6 In prostatic segments, noradrenaline produced inhibition of field stimulation-induced twitches. Its potency was similar in both operated and unoperated preparations, and nisoxetine (0.1 mumol/l) potentiated its effects to a similar extent (approximately 70-fold) in control and operated tissues. Responses to KCl in this half of the vas deferens were essentially unaffected by vasectomy. 7 Taken together, these findings indicate that post-ganglionic denervation of the epididymal half of the rat vas deferens by medial transection (vasectomy) leads to a slowly developing and prolonged supersensitivity to noradrenaline which is primarily due to the loss of the neuronal uptake facility. Persistent adaptive changes in the effector cells are apparently minimal after this means of denervation.

Possible relationship between the release of calcium ions and inactivation of the potassium conductance induced by noradrenaline in smooth muscle of the guinea-pig vas deferens.

In order to examine whether any change in cytoplasmic Ca2+ concentration occurs during the noradrenaline (NA)-induced change in the membrane potential, the isometric tension of smooth muscle of the guinea-pig vas deferens was recorded together with membrane potentials using the sucrose-gap method. NA induced a depolarization and an increase in cytoplasmic Ca2+ comprising two (initial and second) phases. In time courses, the depolarization and the second phase of the increase in cytoplasmic Ca2+ were similar. Only at the phase around the onset of the depolarization, the membrane conductance was increased but then, it was decreased. Lowering the external Ca2+ concentration and application of D600 suppressed all of the NA-induced responses. In addition, D600 diminished the size of the NA-induced decrement in the membrane conductance. The present results suggest that the initial phase of the increase in the cytoplasmic Ca2+ is due to the influx of Ca2+ and the second phase, probably to the release of Ca2+ from some intracellular stores. It was discussed that the release of Ca2+ might occur at the internal surface of the membrane, and the membrane might be left less permeable to K+ as a result.

Evidence for suppression of potassium conductance by noradrenaline in smooth muscle of guinea-pig vas deferens.

The ionic dependency was examined in the reversal potential of the NA-induced membrane depolarization of smooth muscle of the guinea-pig vas deferens, using the double sucrose-gap method. In the control (5.9 mM K) solution and solutions containing 20 and 60 mM K ions, replaced with equimolar amount of Na ions, the reversal potential was negative to the membrane potential at the steady state in each solution, by 19.5, 15.1 and 13.2 mV, respectively. Taking account that the higher external K concentration causes the larger membrane depolarization, these results indicate that the reversal potential shifted toward the positive direction as the external K concentration was increased. On the other hand, the calculated equilibrium potential of K ions in those solutions is -88, -52 and -24 mV, respectively. In those solutions, furthermore, the equilibrium potential of Na ions is 42, 38 and 29 mV, respectively. However, the equilibrium potentials of Ca and Cl ions should be unchanged. Therefore, it is suggested that the reversal potential of the NA-induced depolarization varied in the given different solutions compatibly only with the change in the K equilibrium potential. This provides evidence that in this tissue, NA induces a reduction in the K conductance of the cell membrane.