Is the attenuation of beta-adrenergic agonist efficacy during labor caused by elevated prostaglandin E levels?

Abstract

Our purpose was to investigate whether attenuation of beta-adrenergic agonist efficacy during labor is due to elevated prostaglandin E levels. beta-Receptor function (response to beta-agonist or forskolin) was tested in mononuclear leukocytes collected from women at term before or during labor. beta-Receptor function was also tested in mononuclear leukocytes of nonlaboring patients after in vitro incubation with oxytocin (1 micromol/L), prostaglandin E2 (10 micromol/L), prostaglandin F2alpha (10 micromol/L), or buffer alone. Mononuclear leukocytes from women in active labor exhibited a significant attenuation of beta-adrenergic receptor function as a result of reduced adenylyl cyclase activity. This effect could be induced in mononuclear leukocytes from nonlaboring women by preincubation with prostaglandin E but not oxytocin or prostaglandin F. Prostaglandin E induces heterologous desensitization of the beta-adrenergic receptor system in mononuclear leukocytes, comparable to that seen during labor. We speculate that during labor the elevated levels of prostaglandin E may induce similar effects on the myometrium, thereby decreasing the efficacy of beta-agonists as tocolytics.