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Neurochemical Research

, Volume 33, Issue 7, pp 1292–1300 | Cite as

Norepinephrine-mediated Regulation of 5HT1 Receptor Functioning in Human Platelets

  • M. L. Trincavelli
  • S. Cuboni
  • M. Montali
  • S. Santaguida
  • A. Lucacchini
  • C. MartiniEmail author
Original Paper

Abstract

Adaptive changes in serotonergic 5HT1 receptor signalling are believed to underlie the therapeutic effectiveness of antidepressant drugs. Since cells are continuously exposed to neurotransmitters/neuromodulators, spatially and temporally integrated, the responsiveness of a receptor system is dependent upon the physio-pathological state of the cell and the interaction between different neurotransmitters. In the present work, we investigated heterologous regulation of 5HT1 receptors induced by norepinephrine (NE) in human platelets. NE platelet treatment induced a time and concentration dependent 5HT1 receptor desensitisation mediated by both alpha and beta receptors through activation of intracellular protein kinases. In particular NE, through PKC activation, regulated 5HT1 receptor phosphorylation on threonine residues, causing in turn serotonin receptor-G protein uncoupling and functional responsiveness drop. These results suggest that high NE levels (released i.e. during stress disorders) may play an important role in regulating the 5HT1 responsiveness and in controlling effectiveness of drugs acting on these neurotransmitter systems.

Keywords

5HT1 receptors Human platelets Receptor desensitisation Norepinephrine Adrenergic receptors 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • M. L. Trincavelli
    • 1
  • S. Cuboni
    • 1
  • M. Montali
    • 1
  • S. Santaguida
    • 1
  • A. Lucacchini
    • 1
  • C. Martini
    • 1
    Email author
  1. 1.Department of Psychiatry, Neurobiology, Pharmacology and BiotechnologyUniversity of PisaPisaItaly

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