Decrease in myometrial beta-adrenergic receptors with prenatal cocaine use.

OBJECTIVE: To determine if cocaine use during pregnancy is associated with a reduction in the number or affinity of beta-adrenergic receptors in human myometrium. METHODS: Myometrium was obtained at cesarean delivery of five women who reported using cocaine during pregnancy and from ten controls. Saturation binding assays were performed on the myometrial membrane fractions using [125I]-cyanopindolol to determine beta-adrenergic receptor concentration and affinity. The percentages of beta 1- and beta 2-adrenergic receptors were determined in three cocaine users and four control patients by performing competition binding assays using the beta 2 antagonist ICI 118,551. Results were compared using unpaired Student t tests. RESULTS: Women who reported using cocaine during pregnancy had a significantly lower mean (+/- standard deviation) concentration of myometrial beta-adrenergic receptors than did controls (22 +/- 8 versus 52 +/- 23 fmol/mg protein, respectively). There was no difference in the receptor affinity constants between cocaine users and controls (16 +/- 2 pmol/L for both groups). The percentages of beta 1- and beta 2-adrenergic receptors in the myometrium of the cocaine-use group and control group were similar: 86 +/- 1% beta 2 in the cocaine-use group and 83 +/- 7% beta 2 in the control group. CONCLUSION: Cocaine use during pregnancy may be associated with a down-regulation of beta-adrenergic receptors in human myometrium. This could result in a decreased capacity for uterine relaxation and, consequently, a predisposition to preterm labor.

Characterization of the effect of cocaine on catecholamine uptake by pregnant myometrium.

OBJECTIVE: To characterize the effect of cocaine on catecholamine uptake by myometrium from pregnant women. METHODS: Slices of myometrium obtained from nine women during elective cesarean delivery at term were incubated with [3H]-norepinephrine and various uptake inhibitors for 30 minutes. The radiolabeled material was extracted with perchloric acid, expressed as percent control (+/- standard error of the mean), and compared by one-factor analysis of variance and Fisher multiple range test. RESULTS: Myometrial uptake was inhibited by cocaine (42 +/- 9%) by neuronal (type 1) uptake inhibitors (desipramine 41 +/- 14%; N-ethylmaleimide 53 +/- 8%), and by extraneuronal (type 2) inhibitors (normetanephrine 56 +/- 19%; corticosterone 73 +/- 9%). When uptake inhibitors were used in combination with cocaine, uptake was not decreased further in the presence of neuronal inhibitors (desipramine plus cocaine 40 +/- 20%; N-ethylmaleimide plus cocaine 42 +/- 4%). However, the effect of cocaine appeared to be added to that of extraneuronal inhibitors (normetanephrine plus cocaine 25 +/- 14%; corticosterone plus cocaine 32 +/- 1%). CONCLUSION: Catecholamine uptake by myometrium in pregnant women appears to be both extraneuronal and neuronal in nature, and cocaine inhibits the neuronal portion of this uptake. This mechanism may play a role in the increased rate of premature delivery associated with cocaine abuse.