Abstract
1. The effect of catecholamines (adrenaline, noradrenaline, and isoprenaline) in combination with α- and β-blocking agents (phentolamine and propranolol) on pregnant mouse myometrium was investigated. The catecholamines had an inhibitory action in this tissue, the minimal dose required to produce inhibition being 3×10-9 (g/ml) for isoprenaline, <10-7 for adrenaline, and <10-6 for noradrenaline. While β-adrenergic blocking agent antagonized the inhibitory action of the catecholamines, α-blocking agent did not.
2. Catecholamines produced a hyperpolarization of the membrane and hence spontaneous activity was inhibited. External current stimulation produced a spike potential with an amplitude comparable to that in Krebs solution. During hyperpolarization, there was no statistically significant change in membrane resistance, nor was there a difference between the effects of noradrenaline and isoprenaline.
3. When spontaneous activity was present in normal or low-Na (about 10mM) solution, isoprenaline (10-8g/ml) abolished it. Depolarization and contracture evoked in zero Na (replacement with Tris or sucrose) were restored to normal by isoprenaline, and a spike potential was evoked which was bigger than that in Krebs solution. The existence of external Ca was essential to production of the repolarization.
4. From the above results, a tentative hypothesis on the mechanism of action of catecholamines on pregnant mouse uterus was made as follows:(i) Hyperpolarization, which is responsible for the inhibitory action, is due either to an acceleration of electrogenic Na pumping or to a change in the interaction between the membrane and extracellular, as well as intracellular, Ca.(ii) Isoprenaline reduces [Ca] i, hence abolishing the contracture in zero Na. This may also lead to the production of an action potential in Na-free solution.
