Adrenal tissue catecholamine synthesis

Oifly very small amoimts of DOPA or DA can be detected in most tissues which contain catecholamines, since these compounds exist only as transient intermediates in catecholamine synthesis. In the adrenal glands, in which the ctmcentia-tions of ADR and NA are very high, small amoimts of DA can be measured. 

The arylamino acid decarboxylase inhibitory action of DL-a-fluoromethyldopa (4.77) has also been described. By affecting the enzyme through covalent binding, this compound completely inhibits both catecholamine and serotonin synthesis. Unlike 6-hydroxydopamine, a-fluoromethyldopa does not destroy the neurons, and unlike reserpine it does not deplete chromaffin tissue in the adrenal gland. 

Cyclic AMP can affect the synthesis of catecholamines by two separate modes of action on the rate-limiting catecholamine-synthesizing enzyme tyrosine hydroxylase. Cyclic AMP-dependent kinase can phosphorylate tyrosine hydroxylase, which in turn results in activation of the enzyme. Furthermore, in peripheral tissues such as the adrenal medulla, cAMP can result in the de novo synthesis of tyrosine hydroxylase by causing a derepression of gene expression due to the translocation of the catalytic subunit of the kinase to the chromaffin cell nucleus. 

Epinephrine and norepinephrine are catecholamines which, when released from presynaptic nerve endings, function as neurotransmitters (see here). When released from adrenal medulla in response to low blood glucose levels, epinephrine interacts with second-messenger systems in many tissues, with varied effects. In muscle, epinephrine activates adenylate cyclase, with concomitant activation of glycogenolysis and inhibition of glycogen synthesis. 

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