Cocaine abuse is associated with premature labor, Although cocaine is
known to competitively inhibit beta-adrenergic receptor binding, cocai
ne's effect on receptor downregulation is uncertain, This study was de
signed to determine the in vitro effect of cocaine on downregulation o
f beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myo
metrium was incubated with either cocaine, isoproterenol, or a cocaine
metabolite, benzoylecgonine. Membrane fractions were assayed for beta
-adrenergic receptors using (I-125)-cyanopindolol and the beta(2)-adre
nergic 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 downreg
ulation by isoproterenol. The 46% decrease in beta-adrenergic receptor
s 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 abu
se with premature labor.