Ethodin: pharmacological evidence of the interaction between smooth muscle and mast cells in the myometrium.

Ethodin has been used to induce labor through a mechanism that does not involve the estrogen-preparatory process being postulated as necessary for ensuring the events in a normal labor. The cellular mechanisms involved in that process are unknown. We used an isolated organ bath preparation for mouse uterine horns and a primary culture of mouse myometrial smooth muscle cells to analyze the cellular mechanisms involved in the contractile action of this drug in the myometrium. Ethodin at a concentration of 10 microM and Compound 48/80 (1 microg/ml) evoked contractions of uterine horns in an isolated organ bath preparation. Uterine contractile responses showed a transient increase in contractile tension that lasted 2 to 3 min. Tachyphylaxis was observed after four or five successive stimuli, which consisted in additions and washings of the drug at an interval of 10 min. The primary smooth muscle mouse myometrium cells contained a high proportion of relaxed cells that varied widely in length (5-160 microm). Cell lengths decreased in response to the application of serotonin (10 microM) and oxytocin (0.1 microM) but were not affected after the addition of ethodin (10 microM). However, the cells contracted after a purified fraction of mast cells that had been degranulated by the action of the drug ethodin, which was added to the culture medium. These results provide some evidence related to the mechanism of myometrial contractile action of ethodin and support the hypothesis that mast cells may be involved in the regulation of myometrium contractility.