Abstract
Histamine N-methyltransferase (HNMT) catalyzes the Nτ-methylation of histamine and structurally-related compounds. Levels of HNMT activity in the human red blood cell are regulated by inheritance. The inbred mouse is an ideal laboratory animal in which to study the genetics of inherited traits. Therefore, HNMT activity was measured in renal homogenates of A/J mice to establish optimal assay conditions and to determine the properties of mouse kidney HNMT as a first step toward testing the hypothesis that large strain-related variations in HNMT activity might exist among inbred strains of mice. ApparentK m values for histamine and S-adenosyl-l-methionine, the two cosubstrates for the reaction, were 26 and 1.7 μM, respectively. IC50 values for the inhibition of mouse kidney HNMT by amodiaquine and S-adenosyl-l-homocysteine were 1.67 and 11.8 μM, respectively. HNMT activity levels were then measured under optimal assay conditions in renal preparations from male animals of eleven inbred mouse strains chosen because of the availability of recombinant inbred (RI) animals derived from the parental strains. Average values for renal HNMT activity varied among strains by less than two-fold and ranged only from 26.2±0.51 (mean±SEM) units/mg protein in AKR/J mice to 39.1±2.58 units/mg protein in C57BL/6J animals. Renal HNMT activities in females of the three strains in which both sexes were studied were 11–13% higher than were those in renal tissue from males of the same strain. In summary, the properties of HNMT in the mouse kidney are similar to those of HNMT in other species, but strain variation in levels of enzyme activity among the 11 inbred mouse strains studied was insufficient for these animals to be used in biochemical genetic experiments.
Similar content being viewed by others
Abbreviations
- HNMT:
-
Histamine N-methyltransferase
- Ado-Met:
-
S-adenosyl-l-methionine
- Ado-Hcy:
-
S-adenosyl-l-homocysteine
- RBC:
-
red blood cell
- RI:
-
recombinant inbred
- BSA:
-
bovine serum albumin
- DTT:
-
dithiothreitol
- HPLC:
-
high performance liquid chromography
- DAO:
-
diamine oxidase
- MAO:
-
monoamine oxidase
References
D. D. Brown, R. Tomchick and J. Axelrod,The distribution and properties of a histamine-methylating enzyme. J. Biol. Chem.234, 2948–2950 (1959).
R. J. Harvima, E. O. Kajander, I. T. Harvima and J. E. Fraki,Purification and partial characterization of rat kidney histamine N-methyltransferase. Biochim. biophys. Acta841, 42–49 (1985).
M. A. Beaven,Factors regulating availability of histamine at tissue receptors. InPharmacology of histamine receptors (Eds. C. R. Ganellin and M. E. Parsons) pp. 103–145, Wright PSG, Boston, 1982.
H. Pollard, S. Bischoff and J.-C. Schwartz,Turnover of histamine in rat brain and its decrease under barbiturate anesthesia. J. Pharmac. Exp. Ther.190, 88–99 (1974).
J.-C. Schwartz,Histaminergic mechanisms in brain. Ann. Rev. Pharmac. Ther.17, 325–339 (1977).
J. Axelrod and C. K. Cohen,Methyltransferase enzymes in red blood cells. J. Pharmac. Exp. Ther.176, 78–84 (1970).
J. A. Van Loon, P. A. Pazmiño and R. M. Weinshilboum,Human erythrocyte histamine N-methyltransferase: radiochemical microassay and biochemical properties. Clin. chim. Acta149, 237–251 (1985).
M. C. Scott, J. A. Van Loon and R. M. WeinshilboumPharmacogenetics of N-methylation: heritability of human erythrocyte histamine N-methyltransferase activity. Clin. Pharmac. Ther.43, 256–262 (1988).
P. L. Altman and D. D. Katz,Inbred and genetically defined strains of laboratory animals. Part 1. Mouse and rat. Fed. Am. Soc. Exp. Biol. Bethesda, MD 1979.
J. Staats,Inbred and segregating inbred strains. InThe mouse in biomedical research, vol. 1. History, genetics and wild mice (Ed. H. L. Foster, J. D. Small and J. G. Fox) pp. 123–177, Academic Press, New York 1981.
D. W. Bailey,Recombinatn inbred strains. Transplantation11, 325–327 (1971).
D. W. Bailey,Recombinatn inbred strains and bilineal congenic strains in the mouse. InThe mouse in biomedical research, vol. 1. History, genetics and wild mice (Eds. H. L. Foster, J. D. Small and J. G. Fox) pp. 223–239, Academic Press, New York 1981.
R. R. Bowsher, K. M. Verburg and D. P. Henry,Rat histamine N-methyltransferase. J. biol. Chem.258, 12215–12220 (1983).
M. M. Bradford,A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem.72, 248–254 (1976).
J. C. Robert, J. Vatier, B. K. Nguyen Phuol and S. Bonfils,Determination of histamine, methylhistamines and histamine-O-phthaldialdehyde complexes by two high performance liquid chromatographic procedures. J. Chromatogr.273, 275–287 (1983).
G. N. Wilkinson,Statistical estimations in enzyme kinetics. Biochem. J.80, 324–332 (1961).
W. W. Cleland,Computer programmes for processing enzyme kinetic data. Nature (Lond.)198, 463–465 (1963).
J. P. Green, G. D. Prell, J. K. Khandelwal and P. Blandinn,Aspects of histamine metabolism. Agents and Actions22, 1–15 (1989).
L. B. Hough and E. F. Domino,Tele-methylhistamine oxidation by type B monoamine oxidase. J. Pharmac. Exp. Ther.208, 422–428 (1979).
R. Kapeller-Adler,Amine oxidases and methods for their study. pp. 91–94, Wiley-Interscience, New York 1970.
J. A. Fuentes and N. H. Neff,Selective monoamine oxidase inhibitor drugs as aids in evaluating the role of type A and B enzymes. Neuropharmac.14, 819–825 (1975).
R. M. Weinshilboum and F. A. Raymond,Calcium inhibition of rat liver catechol O-methyltransferase. Biochem. Pharmac.25, 573–579 (1976).
J. Axelrod and J. Tomchick,Enzymatic O-methylation of epinephrine and other catechols. J. Biol. Chem.233, 702–705 (1958).
L. C. Woodson, M. M. Ames, C. D. Selassie, C. Hansch and R. M. Weinshilboum,Thiopurine methyltransferase: aromatic thiol substrates and inhibition by benzoic acid derivatives. Mol. Pharmac.24, 471–478 (1983).
R. M. Weinshilboum, S. Sladek and S. Klumpp,Human erythrocyte thiol methyltransferase: radiochemical microassay and biochemical properties. Clin. chim. Acta97, 59–71 (1979).
H. Barth, I. Niemeyer and W. Lorenz, Speculations about the binding sites of S-adenosyl-l-methionine and some of its synthetic analogues to histamine methyltransferase. Agents and Actions4, 186–188 (1974).
R. T. Borchardt,Synthesis and biological activity of analogs of adenosylhomocysteine as inhibitors of methyltransferases. InBiochemistry of adenosylmethionine (Eds. F. Salvatore, E. Borek, V. Zappia, H. G. Williams-Ashman, F. Schlenk) pp. 151–171, Columbia University Press, New York 1977).
V. H. Cohn,Inhibition of histamine methylation by antimalarial drugs. Biochem. Pharmac.14, 1686–1688 (1965).
N. Barth, W. Lorenz and H. Troidl,Effect of amodiaquine on gastric histamine methyltransferase and on histamine-stimulated gastric secretion. Br. J. Pharmac.55, 321–327 (1975).
R. Weinshilboum,Pharmacogenetics of methylation: relationship to drug metabolism. Clin. Biochem.21, 201–210 (1988).
R. Weinshilboum,Methyltransferase pharmacogenetics. Pharmac. Ther.43, 77–90 (1989).
R. M. Weinshilboum, F. A. Raymond and M. Frohnauer,Monogenic inheritance of catechol O-methyltransferase in the rat: biochemical and genetic studies. Biochem. Pharmacol.28, 1239–1248 (1979).
D. M. Otterness and R. M. Weinshilboum,Mouse thiopurine methyltransferase pharmacogenetics: monogenic inheritance. J. Pharmac. Exp. Ther.240, 817–824 (1987).
S. H. Snyder and J. Axelrod,Sex differences and hormonal control of histamine methyltransferase activity. Biochim. biophys. Acta111, 416–421 (1965).
Author information
Authors and Affiliations
Additional information
This work was supported in part by NIH grants GM 28157, GM 35720, HL 07269 and NIH contract ES 55110 as well as grants from the Burroughs Wellcome Fund and from Squibb Pharmaceuticals.
Rights and permissions
About this article
Cite this article
Scott, M.C., Guerciolini, R., Szumlanski, C. et al. Mouse kidney histamine N-methyltransferase: Assay conditions, biochemical properties and strain variation. Agents and Actions 32, 194–202 (1991). https://doi.org/10.1007/BF01980873
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01980873