Is the attenuation of beta-adrenergic agonist efficacy during labor caused by elevated prostaglandin E levels?
OBJECTIVE
Our purpose was to investigate whether attenuation of beta-adrenergic agonist efficacy during labor is due to elevated prostaglandin E levels.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lye
S J
SJ
Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Bernstein
P
P
Oskamp
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007743:Labor, Obstetric / Q000097:blood / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects; D010120:Oxytocics / Q000494:pharmacology; D011247:Pregnancy; D011458:Prostaglandins E / Q000097:blood*; D013997:Time Factors; D015149:Tocolytic Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D010120:Oxytocics; D011458:Prostaglandins E; D015149:Tocolytic Agents; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007545:Isoproterenol