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 serotonin) and type A-B (dopamine, tyramine and kynuramine) substrates, and is selectively inhibited by clorgyline (IC50 approximately 10(-6) 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, 1-deprenyl (IC50 approximately 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 Km values of 400, 280, 170 and 227 microM for noradrenaline, dopamine, serotonin and tyramine. The apparent Km value for phenylethylamine is 235 microM. On the other hand, isolated chromaffin cells have the B form of monoamine oxidase with high affinity (Km approximately 25 microM) for phenylethylamine and low affinities for noradrenaline (Km approximately 1100 microM) and adrenaline (Km approximately 1700 microM). This enzyme form is selectively inactivated by the monoamine oxidase type B inhibitor, 1-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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000310:Adrenal Gland Neoplasms; D000313:Adrenal Medulla / Q000378:metabolism; D000320:Adrenergic Fibers; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D008995:Monoamine Oxidase / Q000378:metabolism*; D010673:Pheochromocytoma; D011188:Potassium / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology*
D002395:Catecholamines; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D011188:Potassium; D014439:Tyramine