THE EFFECT OF COCAINE ON CATECHOL-O-METHYL-TRANSFERASE AND ON THE RESPONSE TO NOREPINEPHRINE OF RABBIT AORTIC STRIPS

Abstract

The ability of cocaine to produce supersensitivity of catecholamines has been demonstrated in a variety of adrenergically innervated systems. The mechanism of this supersensitivity is generally thought to involve impairment of amine uptake by the adrenergic nerves resulting in a shift of the amine from the nerve endings to the receptors and a consequent increase in the response of the effector organ or supersensitivity. Contrary to this, several investigators have recently suggested that the sensitizing action of cocaine on the blood vessels cannot be attributed entirely to its ability to inhibit the uptake of the amine (1–5). Cold storage preparations have shown such supersensitivity without the inhibition of amine uptake (3). Kalsner and Nickerson (5) point out that enzymatic pathways are as important in the inactivation of physiological concentrations of amines as the amine uptake mechanisms, the site of the sensitizing action probably being post synaptic. Previous data indicated that the catechol-O-methyltransferase (COMT) inhibitor, pyrogallol, but not the monoamine oxidase (MAO) inhibitors (tranylcypromine and iproniazid), potentiated the response of rabbit aortic strips to norepinephrine (7, 8). However, there appears to be little known for an inhibitory action of cocaine on the extracellular norepinephrine-metabolizing enzyme, catechol-O-methyltransferase (9). The present study was therefore undertaken to investigate the relationship between the effect of cocaine on the COMT activity and the potentiation of norepinephrine-induced contraction.