Tetrahydroisoquinolinecarboxylic acids and regulation of phenylethanolamine N-methyltransferase in cultured adrenal medulla

Abstract

Explants of rat adrenal medullae, cultured for up to 48 hr in the presence of 3′,4′-deoxynorlaudanosolinecarboxylic acid (DNLCA) or α-methyltyrosine, exhibited a 69% increase in phenylethanolamine N-methyltransferase (PNMT) activity as measured in dialyzed homogenates. A related tetrahydroisoquinoline, norlaudanosolinecarboxylic acid (NLCA), when added to the medium did not elevate PNMT activity. No increase in the amount of PNMT was detected by immunochemical titration of homogenates from DNLCA-treated cultured medulla, nor were there changes in rates of synthesis or degradation of the enzyme. Although DNLCA is an inhibitor of tyrosine 3-monooxygenase, it had no effect on PNMT activity when added directly to an incubation mixture in vitro. Kinetic analyses of dialyzed homogenates from explants cultured in the presence of DNLCA revealed that the V max of PNMT was higher than that of control tissue. There was no decrease in K m after DNLCA treatment. The increase in PNMT activity appears to be a compensatory response to depletion of medullary catecholamines by DNLCA or α-methyltyrosine.