Wang F L, Gauvin J M, Dombrowski M P, Smith Y R, Christopher K A, Hurd W W
Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, USA.
Reprod Toxicol. 1996 Mar-Apr;10(2):119-23. doi: 10.1016/0890-6238(95)02053-5.
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.
可卡因滥用与早产有关。尽管已知可卡因可竞争性抑制β-肾上腺素能受体结合，但其对受体下调的影响尚不确定。本研究旨在确定可卡因对妊娠子宫肌层中β-肾上腺素能受体下调的体外作用。将妊娠绵羊的子宫肌层与可卡因、异丙肾上腺素或可卡因代谢物苯甲酰芽子碱一起孵育。使用（125I）-氰基吲哚洛尔和β2-肾上腺素能拮抗剂ICI 118,551对膜分离物进行β-肾上腺素能受体检测。我们发现，可卡因（10^(-6)至10^(-4)mol/L）而非苯甲酰芽子碱可下调β1-和β2-肾上腺素能受体，但不会进一步增强异丙肾上腺素引起的受体下调。暴露于可卡因后观察到的β-肾上腺素能受体减少46%与异丙肾上腺素后观察到的减少53%相似。我们推测，可卡因对β-肾上腺素能受体的下调可能在可卡因滥用与早产的关联中起作用。
