Cocaine-Induced Supersensitivity in the Human Umbilical Artery

Cocaine (3.3 × 10−7 – 3.3 × 10−5 M) has no effect on the uptake of noradrenaline by the smooth muscle cells of the human umbilical artery but was found to potentiate the mean effective dose (ED50) responses of isolated helical strips of human umbilical artery to noradrenaline (3 × 10−5 M), and, to a lesser degree, 5-hydroxytryptamine (3.65 × 10−4 M), but had no effect on the response to KCl (40 mM) or histamine (1.8 × 10−6 M). Concentrations of cocaine above 1.7 × 10−4 M were found to antagonize ED50 responses to all the agonists tested. Because the preparation used in these studies does not receive sympathetic innervation, the effect of cocaine is likely to be mediated by an action at the level of the muscle. This selective increase in the response mediated by noradrenaline may be explained by an allosteric alteration of the α-adrenergic receptor system and/or a semiselective increase in smooth muscle sensitivity.