Abstract
We have previously reported histamine desensitization of human blood mononuclear leukocytes resulting in reduced cAMP responses to β-adrenergic agonists, histamine and prostaglandin E1. This heterologous desensitization occurred at low, micromolar histamine concentrations and was accompanied by elevation of cAMP-phosphodiesterase (PDE) activity in these cells. We have now investigated the activity of PDE in the lymphocyte and monocyte fractions of mononuclear leukocytes to determine the site of histamine effect.
PDE activity per cell was higher in monocytes (0.075±0.070 units) than lymphocytes (0.026±0.08) units). Monocytes responded to 10−6 M histamine stimulation with a much greater increase in PDE activity (0.354±0.1 units) than did lymphocytes (0.047±0.015 units). Histamine receptor studies, using thiazolylethylamine and chlorpheniramine as H1-agonist and antagonist respectively and dimaprit and cimetidine as H2-agonists and antagonists respectively, indicated that the histamine stimulation of PDE activity is mediated predominantly through H1 histamine receptor in the monocytes and the H2 receptor in the lymphocytes. Previously histamine had been thought to increase cyclic AMP by acting on H2 receptors to activate adenylate cyclase. Our studies show that stimulation of H1 or H2 receptors by low histamine concentration can cause the opposite effect i.e. increased catabolism and a net reduction in cAMP levels. The localization of this effect predominantly to monocytes indicates a potentially important mechanism for histamine action on immune regulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
D. M. Chuang, J. K. William, L. Farber and E. Costa,Biochemical study of receptor internalization during β-adrenergic receptor desensitization in frog erythrocytes. Mol. Pharm.18, 348–355 (1980).
P. H. Scarpace and B. A. Itamar,Desensitization of adenylate cyclase and down regulation of beta adrenergic receptors after in vivo administration of beta agonist. J. Pharm. Exp. Ther.223, 327–331 (1982).
R. J. Lefkowitz, D. Mullikir and M. G. Caron,Regulation of β-adrenergic receptors by guanly-5'yl imidodiphosphate and other purine nucleotides. J. Biol. Chem.251, 4868–4692 (1976).
J. A. Beavo, R. S. Hansen, S. A. Harrison, R. L. Hurwitz, T. J. Martins and M. C. Mumby,Identification and properties of cyclic nucleotide phosphodiesterase. Mol. Cell. Endocrin.28, 387–410 (1982).
W. J. Thompson, C. P. Ross, W. J. Pledger and S. J. Strada,Cyclic adenosine 3′, 5′-monophosphate phosphodiesterase: distinct forms in human lymphocytes and monocytes. J. Biol. Chem.251, 4922–4929 (1976).
J. H. Wedner, Y. C. Bruno, C. S. Parker and C. W. Parker,Cyclic nucleotide phosphodiesterase activity in human peripheral blood lymphocytes and monocytes. J. Immunol.123, 725–732 (1979).
S. C. Chan, S. R. Grewe, S. R. Stevens and J. M. Hanifin,Functional desensitization due to stimulation of cyclic AMP-phosphodiesterase in human mononuclear leukocytes. J. Cyclic Nucleotide Res.8, 211–224 (1982).
F. Gmelig-Meyling and N. Waldman,Separation of human blood monocytes and lymphocytes on a continuous percoll gradient. J. Immunol. Methods33, 1–9 (1980).
N. A. Pawlowski, G. Kaplan, A. L. Hamill, L. A. Cohn and W. Scott,Arachidonic acid metabolism by human monocytes: Studies with platelet depleted culture. J. Exp. Med.158, 393–412 (1983).
L. T. Yam, C. Y. Li and W. H. Crosby,Cytochemical identification of monocytes and granulocytes. Amer. J. Clin. Path.55, 283–290 (1971).
W. J. Thompson, W. L. Terasaki, P. M. Epstein and S. J. Strada,Assay of cyclic nucleotide phosphodiesterase and resolution of multiple forms of the enzyme. Adv. Cyclic Nucleotide Res.10, 69–82 (1980).
J. P. Moore, G. A. Smith, R. Hesketh and J. C. Metcalfe,Large effects of preparative techniques on lymphocyte cyclic AMP content. Biochem. J.216, 207–213 (1983).
S. M. Matloff, I. K. Kiselis and R. E. Rocklin,Reduced production of histamine induced suppressor factor (HSF) by atopic mononuclear cells and decreased prostaglandin E output by HSF-stimulated atopic monocytes. J. Allergy Clin. Immunol.72, 359–364 (1983).
T. A. Guistina, S. C. Chan, J. W. Baker and J. M. Hanifin,Increased leukocyte sensitivity to PDE inhibitors in atopic dermatitis. J. Allergy Clin. Invest.74, 252–257 (1984).
S. C. Chan, D. Trask, S. Shermann and J. M. Hanifin,Protein kinase C phosphorylation of a membrane precursor may account for increased cyclic AMP phosphodiesterase activity in atopic dermatitis monocytes. J. Invest. Dermatol. (1986) in press.
H. R. Bourne, G. M. Tomkins and A. Dion,Regulation of phosphodiesterase synthesis: requirement for cyclic adenosine monophosphate-dependent protein kinase. Science181, 952–954 (1973).
D. R. Bristow, J. R. Hare Jr., J. R. Hearn and L. E. Martin,Radioligand binding studies using (3 H)-cimetidine and (3 H)-ranitidine. Br. J. Pharmacol.72, 547 (1981).
D. B. Norris, T. J. Rising, S. E. Warrander and T. P. Wood, (3H)-cimetidine binding in guinea pig gastric mucosa. Br. J. Pharmacol.72, 548 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Holden, C.A., Chan, S.C., Norris, S. et al. Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. Agents and Actions 22, 36–42 (1987). https://doi.org/10.1007/BF01968814
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01968814