Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes

C. A. Holden, S. C. Chan, S. Norris, J. M. Hanifin

Research output: Contribution to journalArticle

20 Scopus citations

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 1 1987

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes'. Together they form a unique fingerprint.

  • Cite this