INHERITANCE OF ADRENAL PHENYLETHANOLAMINE N-METHYLTRANSFERASE ACTIVITY IN THE RAT

Jon M. Stolk ¹, Guido Vantini ¹, Ras B. Guchhait ¹, Jeffrey H. Hurst ¹, Bruce D. Perry ², David C. U'Prichard ², and Robert C. Elston ³

¹ Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228
² Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611
³ Department of Biometry, Louisiana State University Medical Center, New Orleans, Louisiana 70112

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-l-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar K_m values for the cosubstrate (S-adenosyl-l-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 x Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.