Summary
The effect of histamine on sterol synthesis has been investigated in freshly isolated human mononuclear leukocytes from healthy subjects.
Incubation of cells for 6 h in a medium containing lipid depleted serum led to a threefold increase in the incorporation of (14C)-acetate or tritiated water into sterols. Histamine 0.3 µM added to the incubation medium at zero time inhibited this induction by 35% with a sigmoidal log dose-effect curve.
The receptors mediating this action were characterised pharmacologically by using selective H1- and H2-agonists and -antagonists. The H2-agonists impromidine and 4-methylhistamine mimicked the effect of histamine on sterol synthesis, the suppression being 42% and 31%, respectively, at a concentration of 1 µM. In contrast, the H1-agonist 2-pyridylethylamine did not affect the pathway. The H2-antagonist cimetidine (10 µM) but not the H1-antagonist mepyramine (10 µM) totally reversed the inhibition of sterol synthesis by histamine.
The results provide evidence that sterol synthesis in human mononuclear leukocytes is regulated by histamine, which appears to act predominantly via H2-receptors.
Similar content being viewed by others
References
Burland WL, Mills JG (1982) The pathophysiological role of histamine and potential therapeutic uses of H1- and H2-antihistamines. In: Ganellin CR, Parsons ME (eds) Pharmacology of histamine receptors. Wright, Bristol London Boston, pp 436–481
Grund VR, Goldberg ND, Hunninghake DB (1975) Histamine receptors in adipose tissue: Involvement of cyclic adenosine monophosphate and the H2-receptor in the lipolytic response to histamine in isolated canine fat cells. J Pharmacol Exp Ther 195: 176–184
Keller MB, Grund VR, Johnson CL (1981) Impromidine stimulated adenylate cyclase activity in canine fat cell ghosts. Pharmacologist 23: 186
Boyüm A (1962) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 97 [Suppl 21]: 77–89
McFarlane AS (1968) Behavior of lipids in human serum. Nature 149: 439
Bligh EG, Dyer WSA (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911–917
Gilmann AG (1970) A protein binding assay for adenosine 3′:5′-cyclic monophosphate. Proc Natl Acad Sci USA 67: 305–312
Brown BL, Albano JDM, Ekins RP, Sgherzi AM (1971) A simple and sensitive saturation assay method for the measurement of adenosine 3′:5′-cyclic monophosphate. Biochem J 121: 561–562
Ho YK, Faust JR, Bilheimer DW, Brown MS (1977) Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes. J Exp Med 145: 1531–1549
Ganellin CR (1982) Chemistry and structure-activity relationship of drugs acting at histamine receptors. In: Ganellin CR, Parsons ME (eds) Pharmacology of histamine receptors. Wright, Bristol London Boston, pp 10–102
Durant GC, Duncan WAM, Ganellin CR, Parsons ME, Blakemore RC, Rasmussen AC (1978) Impromidine (SK & F 92676) is a very potent and specific agonist for histamine H2-receptors. Nature 276: 403–404
Black JW, Duncan WAM, Durant CJ, Ganellin CR, Parsons ME (1972) Definition and antagonism of histamine H2-receptors. Nature 236: 385–390
Johnson CL (1982) Histamine receptors and cyclic nucleotides. In: Ganellin CR, Parsons ME (eds) Pharmacology of histamine-receptors. Wright, Bristol London Boston, pp 146–216
Bourne HR, Melmon KL, Lichtenstein LM (1971) Histamine augments leukocyte adenosine 3′,5′-monophosphate and blocks antigenic histamine release. Science 173: 743–745
Weinstein Y, Melmon KL, Bourne HR, Sela M (1973) Specific leukocyte receptors for small endogenous hormones. J Clin Invest 52: 1349–1361
Marone G, Lichtenstein LM, Plant M (1980) Hydrocortisone and human lymphocytes: Increases in cyclic adenosine 3′:5′-monophosphate and potentiation of adenylate cyclase-activating agents. J Pharmacol Exp Ther 215: 469–478
Krone W, Hildebrandt F, Greten H (1982) Effect of catecholamines on sterol synthesis in human mononuclear cells. Eur J Clin Invest 12: 467–470
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Krone, W., Müller-Wieland, D., Behnke, B. et al. Regulation of sterol synthesis by histamine in human mononuclear leukocytes: Roles of H1- and H2-receptors. Eur J Clin Pharmacol 34, 29–33 (1988). https://doi.org/10.1007/BF01061413
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01061413