Contrasting monoamine oxidase activity and tyramine induced catecholamine release in PC12 and chromaffin cells

PC12 (phaeochromocytoma derived) cells possess the catecholamine synthesizing enzymes as well as the ability to store and release the catecholamines in response to K + . However, their monoamine oxidase activity and catecholamine release in response to tyramine has not been examined previously. PC12 cells have monoamine oxidase activity which oxidizes type A (noradrenaline and serolonin) and type A-B (dopamine, tyramine and kynuramine) substrates, and is selectively inhibited by clorgyline ( ic 50 ~ 10 −8 M ). In contrast, PC12 cell monoamine oxidase hardly oxidizes phenylethylamine, a type B substrate, and is relatively insensitive to inhibition by the selective monoamine oxidase type B inhibitor. I-deprenyl ( ic 50 ~ 10 −6 M ). By the above criteria it is apparent that the monoamine oxidase in PC12 is solely type A. The kinetics of the oxidase are similar to those of monoamine oxidase type A reported in other tissues including the adrenergic neuron, having apparent K m values of 400, 280, 170 and 227 μM for noradrenaline, dopamine, serotonin and tyramine. The apparent K m value for phenylethylamine is 235 μM. On the other hand, isolated chromaffin cells have the B form of monoamine oxidase with high affinity ( K m ~25μM) for phenylethylamine and low affinities for noradrenaline ( K m ~ 1100μ M) and adrenaline ( K m ~ 1700/gmM). This enzyme form is selectively inactivated by the monoamine oxidase type B inhibitor, I-deprenyl. In similar fashion to peripheral adrenergic neurons, PC12 cells share the capacity to express a tyramine releasable pool of catecholamines, a property entirely lacking in mature cultured chromaffin cells, even though the latter cells are capable of taking up tyramine by a cocaine sensitive process. However, both PC12 cells and chromaffin cells have a voltage and calcium dependent, K + induced, catecholamine release mechanism. Although previous studies have demonstrated that PC12 cells share some functional and biochemical properties with adrenergic neurons as well as chromaffin cells, the present study indicates that they have a closer resemblance to adrenergic neurons with regard to monoamine oxidase activity and tyramine induced catecholamine release than to chromaffin cells.