Subsensitivity of adenylyl cyclase-coupled receptors on mononuclear leukocytes from drug-free inpatients with a major depressive episode

J. John Mann, James P. Halper, Philip J. Wilner, John A. Sweeney, Tammy A. Mieczkowski, Jaw Sy Chen, Peter E. Stokes, Richard P. Brown

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Previous studies have demonstrated blunted beta-adrenergic responsivity in leukocytes from depressed patients. We sought to determine if this blunted cyclic adenosine monophosphate (AMP) response is specific for beta-adrenergic receptors (homologous), or whether other adenylyl cyclase-coupled receptors are also involved (heterologous), in order to localize this effect at the level of the receptor versus the coupling protein or the transducer, adenylyl cyclase. We studied adenylyl cyclase-mediated responses in peripheral blood mononuclear cells from 95 drug-free patients with a major depressive episode and 69 healthy controls. We found a similar degree of decrease in the peak cyclic AMP response to activation of the beta-adrenergic receptor (28%) and the prostaglandin receptor: (34%) in the depressed patients, which indicated heterologous desensitization. Forskolin cyclic AMP responses were not blunted. Blunting of cyclic AMP responses to isoproterenol did not appear to correlate with levels of plasma norepinephrine and epinephrine or hypothalamic-pituitary-adrenocortical function. The absence of a decrease in the peak forskolin-generated cyclic AMP response, which involves direct activation of adenylyl cyclase, suggests an abnormality at the level of the coupling protein in these adenylyl-coupled receptors in depressed patients. Future studies need to determine whether this leukocyte signal transduction defect in depression also involves brain adenylyl cyclase-coupled receptors.

Original languageEnglish (US)
Pages (from-to)859-870
Number of pages12
JournalBiological Psychiatry
Volume42
Issue number10
DOIs
StatePublished - Nov 15 1997

Keywords

  • Adenylyl cyclase
  • Beta- adrenergic
  • Catecholamines
  • Leukocytes
  • Major depression

ASJC Scopus subject areas

  • Biological Psychiatry

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    Mann, J. J., Halper, J. P., Wilner, P. J., Sweeney, J. A., Mieczkowski, T. A., Chen, J. S., Stokes, P. E., & Brown, R. P. (1997). Subsensitivity of adenylyl cyclase-coupled receptors on mononuclear leukocytes from drug-free inpatients with a major depressive episode. Biological Psychiatry, 42(10), 859-870. https://doi.org/10.1016/S0006-3223(97)00154-6