Cocaine downregulates beta-adrenergic receptors in pregnant sheep myometrium.
Cocaine abuse is associated with premature labor. Although cocaine is known to competitively inhibit beta-adrenergic receptor binding, cocaine's effect on receptor downregulation is uncertain. This study was designed to determine the in vitro effect of cocaine on downregulation of beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myometrium was incubated with either cocaine, isoproterenol, or a cocaine metabolite, benzoylecgonine. Membrane fractions were assayed for beta-adrenergic receptors using (125I)-cyanopindolol and the beta 2-adrenergic antagonist ICI 118,551. We found that cocaine (10(-6) to 10(-4) mol/L), but not benzoylecgonine, downregulated both beta 1- and beta 2-adrenergic receptors, but did not further augment receptor downregulation by isoproterenol. The 46% decrease in beta-adrenergic receptors seen after exposure to cocaine was similar to the 53% decrease seen after isoproterenol. We hypothesize downregulation of beta-adrenergic receptors by cocaine may play a role in the association of cocaine abuse with premature labor.
Wang
F L
FL
Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, USA.
Gauvin
J M
JM
Dombrowski
M P
MP
Smith
Y R
YR
Christopher
K A
KA
Hurd
W W
WW
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D007545:Isoproterenol / Q000633:toxicity; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000187:drug effects*; D012756:Sheep
D011943:Receptors, Adrenergic, beta; C005618:benzoylecgonine; D003042:Cocaine; D007545:Isoproterenol