DISPOSITION OF NOREPINEPHRINE AND EPINEPHRINE IN VASCULAR TISSUE, DETERMINED BY THE TECHNIQUE OF OIL IMMERSION

¹ Department of Pharmacology and Therapeutics, University of Manitoba Faculty of Medicine, Winnipeg, Manitoba, Canada

Experiments with the oil-immersion technique demonstrated that Omethylation is the primary enzymatic mechanism for the inactivation of a low concentration (1x10^-8) of both norepinephrine and epinephrine in rabbit aortic strips, but inhibition of catechol-O-methyltransferase slowed the rate of inactivation of norepinephrine considerably less than it did that of epinephrine. Inhibition of monoamine oxidase had a negligible effect on the inactivation of either, if catechol-O-methyltransferase activity was unimpaired. The effects of combinations of inhibitors indicated that catechol-O-methyltransferase and monoamine oxidase function in series, with the latter an effective alternate mechanism for the inactivation of norepinephrine and somewhat less effective for epinephrine. A possible anatomical basis for this behavior is pointed out. Experiments with a 100-fold higher concentration of these catecholamines showed that the major intrinsic pathways of inactivation are deamination and O-methylation for norepinephrine and epinephrine, respectively. It is suggested that the high concentration of agonist swamped the normal, organized system of inactivation, with a more or less simultaneous presentation of amine to both enzymes, which revealed their capacities for handling the two catecholamines. The contributions of binding and storage mechanisms to norepinephrine and epinephrine inactivation were assessed on the basis of the effects of cocaine. These processes were found to be considerably less important than enzymatic pathways in the inactivation of physiologic concentrations of norepinephrine and epinephrine and were found to make only a minor contribution to the inactivation of high concentrations.