NONADRENAL EPINEPHRINE-FORMING ENZYMES IN HUMANS - CHARACTERISTICS, DISTRIBUTION, REGULATION, AND RELATIONSHIP TO EPINEPHRINE LEVELS

被引:42
作者
KENNEDY, B
BIGBY, TD
ZIEGLER, MG
机构
[1] Department of Medicine, University of California, San Diego Medical Center, San Diego
[2] UCSD Medical Center, San Diego, CA 92103-8341
关键词
PNMT; NONSPECIFIC N-METHYL-TRANSFERASE; DEXAMETHASONE; LUNG; RBC;
D O I
10.1172/JCI117996
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Animal studies indicate that nonadrenal tissues may synthesize epinephrine (E), Here we demonstrate phenylethanolamine N-methyltransferase (PNMT) and/or nonspecific N-methyltransferase (NMT) enzymatic activity in human lung, kidney, heart, liver, spleen, and pancreas, There was a significant overall correlation (r = 0.34) between tissue PNMT and E, PNMT and NMT in human tissues differed in substrate and inhibitor specificity, thermal stability, and antigenicity, By these criteria, PNMT in human lung and in human bronchial epithelial cells were indistinguishable from adrenal PNMT. PNMT and/or NMT activity were present in red blood cells (RBCs), and cancer cell lines, Human kidney, lung, and pancreas showed immunohistochemical staining with an antibody to adrenal PNMT, RBC PNMT activity was lower in males than females and was increased in hyperthyroidism and decreased in hypothyroidism, PNMT activity in a human bronchial epithelial cell line was dramatically increased by incubation with dexamethasone, E and H-3-E levels in plasma and urine during an intravenous infusion of H-3-E into humans indicated ghat kidney may synthesize half of urinary E, We conclude that PNMT and NMT are widely distributed in human tissues, that they may synthesize E in vivo and are influenced by glucocorticoid and thyroid hormones.
引用
收藏
页码:2896 / 2902
页数:7
相关论文
共 34 条
[1]  
AXELROD J, 1962, J BIOL CHEM, V237, P1657
[2]  
AXELROD J, 1962, J PHARMACOL EXP THER, V138, P23
[3]  
BARCHAS J D, 1969, Biological Psychiatry, V1, P31
[4]  
Clutter W E, 1980, Prog Biochem Pharmacol, V17, P84
[5]   EPINEPHRINE PLASMA METABOLIC-CLEARANCE RATES AND PHYSIOLOGIC THRESHOLDS FOR METABOLIC AND HEMODYNAMIC ACTIONS IN MAN [J].
CLUTTER, WE ;
BIER, DM ;
SHAH, SD ;
CRYER, PE .
JOURNAL OF CLINICAL INVESTIGATION, 1980, 66 (01) :94-101
[6]   ADRENALINE RELEASE BY THE HUMAN HEART [J].
ESLER, M ;
EISENHOFER, G ;
DART, A ;
CHIN, J ;
COX, H ;
LAMBERT, G ;
JENNINGS, G .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1991, 18 (02) :67-70
[7]   INHIBITION OF RAT-KIDNEY HISTAMINE-N-METHYLTRANSFERASE BY BIOGENIC-AMINES [J].
FUHR, N ;
KOWNATZKI, E .
PHARMACOLOGY, 1986, 32 (02) :114-120
[8]   BIOCHEMICAL-STUDIES OF N-METHYLTRANSFERASE IN HUMAN AND GUINEA-PIG LUNG - NO APPARENT ROLE IN THE PATHOGENESIS OF ASTHMA [J].
HENDERSON, GD ;
RUFFIN, RE ;
ALPERS, JH ;
CROCKETT, AJ ;
SCHEMBRI, DA ;
LATIMER, KM .
CLINICAL SCIENCE, 1988, 75 (01) :5-11
[9]  
HOBEL CJ, 1981, AM J OBSTET GYNECOL, V141, P1009
[10]  
KANEDA N, 1988, J BIOL CHEM, V263, P7672