Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes

C. A. Holden, S. C. Chan, S. Norris, Jon Hanifin

Research output: Contribution to journalArticle

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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 10-6M 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.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalAgents and Actions
Volume22
Issue number1-2
DOIs
StatePublished - Oct 1987

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Phosphoric Diester Hydrolases
Human Activities
Cyclic AMP
Histamine
Monocytes
Lymphocytes
Histamine H2 Receptors
Histamine Agonists
Mononuclear Leukocytes
Histamine H1 Receptors
Dimaprit
Histamine Agents
Chlorpheniramine
Histamine Receptors
Adrenergic Agonists
Alprostadil
Cimetidine
Adenylyl Cyclases
Blood

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)

Cite this

Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. / Holden, C. A.; Chan, S. C.; Norris, S.; Hanifin, Jon.

In: Agents and Actions, Vol. 22, No. 1-2, 10.1987, p. 36-42.

Research output: Contribution to journalArticle

Holden, C. A. ; Chan, S. C. ; Norris, S. ; Hanifin, Jon. / Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. In: Agents and Actions. 1987 ; Vol. 22, No. 1-2. pp. 36-42.
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