The stimulant action of noradrenaline (alpha-action) on guinea-pig myometrium compared with that of acetylcholine.

Abstract

In the smooth muscle of guinea-pig uterus (oestrogen dominated) both noradrenaline (Nor) (α-action) and acetylcholine (ACh) depolarized the membrane, reduced membrane resistance, accelerated spike discharge and increased isometric tension proportionately. The magnitude of the response to ACh was directly related to the dose of ACh, the duration remaining that of the period of drug application. The response to Nor was slow in onset and outlasted the period of drug application by several minutes. Increasing doses of Nor mainly prolonged the duration of the response. The magnitude of the response depended on whether the depolarization by Nor reached firing threshold. The phasic tension response to evoked spikes was increased by Nor. Cooling reduced, and at 6°C abolished the depolarization caused by Nor but did not significantly change the response to ACh. The results obtained with variations of external potassium and chloride indicate that both ACh and Nor increased the membrane permeability to potassium, but that the Nor effect was small and shortlasting. Chloride was not involved in the depolarization caused by ACh, while the magnitude of depolarization and of the increase in membrane conductance by Nor were a direct function of the external chloride concentration. The removal of sodium from the external medium slowed the relaxation of the phasic tension responses to evoked spikes and increased resting tension. In the absence of spikes the tissue relaxed. The depolarization and reduction of membrane resistance by ACh were directly related to the external sodium concentration regardless whether sucrose or tris-Cl were used as substitute. The depolarization and reduction of membrane resistance by Nor did not depend on external sodium (tris substitution) though in the simultaneous absence of sodium and chloride (sucrose substitution) the response to Nor was abolished. The results obtained when NaCl was replaced with tris-Cl suggest that ACh may, in the absence of sodium, increase the entry of calcium. The failure of calcium removal from the cytoplasm may explain the maintained contracture. The contracture produced by Nor was increased in the absence of sodium, suggesting that, in addition to an increased calcium entry from outside, there may have been a release of sequestered calcium.