The functional coupling of neuronal and extraneuronal transport with intracellular monoamine oxidase

Summary

“Metabolizing systems” are responsible for the quick inactivation of noradrenaline released from adrenergic nerve endings: a transport mechanism (uptake¹ or uptake₂) is arranged in series with the intracellular enzyme (monoamine oxidase, MAO; catechol-O-methyltransferase, COMT). In the perfused rat heart, k_enzyme-values were determined, i.e., those rate constants which characterize the unsaturated intracellular enzymes. In the extraneuronal metabolizing system k_comt > k_mao for noradrenaline and adrenaline, while rather similar rate constants were obtained for dopamine. However, for the neuronal deaminating system, k_mao is considerably higher than k_mao for the extraneuronal system. Second, in the rat vas deferens it is demonstrated that inhibition of neuronal MAO leads to very pronounced rises of the axoplasmic noradrenaline concentration—and this is again a reflection of the high activity of neuronal MAO. In a third series of experiments (with the rat vas deferens), the evidence indicates that the neuronal inward transport of substrates of MAO fails to saturate the enzyme. This is the functional consequence of the high activity of neuronal MAO. It is concluded that a) neuronal MAO activity is very high, and—as a consequence—b) axoplasmic noradrenaline levels are very low.

The experiments reported here were supported by the Deutsche Forschungsgemeinschaft (SFB176). — L. C. and A. L. were recipients of Humboldt-Foundation scholarships.