Extra-Adrenal Nonneuronal Epinephrine and Phenylethanolamine-N-Methyltransferase

Abstract

Publisher Summary Phenylethanolamine- N -methyltransferase (PNMT) is an enzyme that specifically methylates P-hydroxylated phenylethanolamines. Epinephrine (Epi) is synthesized in the adrenal from norepinephrine (NE) by this PNMT. NE can also be N-methylated by a less specific N -methyltransferse (NMT) that N-methylates many amines. NMT is distinguished from PNMT by the ability of NMT to convert dopamine into [ 3 H]epinine and by the selective effect of PNMT inhibitors to block N-methylation by PNMT but not by NMT. This chapter summarizes several studies suggesting that Epi has a profound effect on pulmonary function. It stimulates α and β receptors in the lung and has a particularly high affinity for β 2 receptors. Stimulation of pulmonary adrenergic receptors by Epi causes bronchodilation. The Epiforming capacity of lung homogenates has been inhibited by the PNMT inhibitor SKF 29661 about half as well as in adrenal but better than in cardiac ventricle. It appears that 50% of lung Epi-forming activity is from PNMT and 50% from NMT. Studies on Epi-forming activity in human tissues have shown that PNMT and NMT activity is detectable in most tissues. PNMT activity predominates in heart and lung, whereas NMT is more prevalent in kidney, liver, bronchus, and trachea. Overall, tissue Epi levels correlated with PNMT activity but not with NMT. Moreover, human PNMT appears to be responsive to thyroid hormones. Red blood cells (RBC)-PNMT activity has been below normal levels in hypothyroid patients and returned to normal levels when the patients became euthyroid after chronic thyroxin treatment. On the other hand, hyperthyroid subjects have elevated RBC-PNMT activity. NMT activity has not been altered by either hypothyroidism or hyperthyroidism.