Second messenger systems in Tourette's syndrome

Harvey S. Singer, Jeffrey Dickson, Daniel Martinie, Michael Levine

Research output: Contribution to journalArticle

Abstract

Abnormalities within second messenger systems have been hypothesized as the underlying pathophysiologic mechanism in a variety of neuropsychiatric disorders. In the Gilles de la Tourette syndrome (TS) prior studies have shown that the concentration of adenosine 3′,5′-monophosphate (cAMP) is reduced in cortical and putamen brain regions. In this study, postmortem cortical tissues from 4 adults (mean age 59.5 years) with the lifetime diagnosis of TS and 5 controls (mean age 63.8 years) were analyzed for functional activities within the cAMP and phosphoinositide systems. In addition, plasma cAMP was quantified in children with TS (n = 33) and controls (n = 17). In frontal (A4, A6) and occipital (A17) cortical tissues there were no significant differences for adenylyl cyclase activity whether assayed under basal conditions or after stimulation with GTPγS (a non-hydrolyzable GTP analog), forskolin (a selective enzyme stimulator), or (-)-isoproterenol (a β-adrenergic agonist). D2 receptor activation (quinpirole) and assessment of the inhibitory guanine nucleotide protein also showed no significant alterations in TS samples. Activity of cAMP phosphodiesterase was increased insignificantly in A4 and A17 TS brain regions. Plasma concentrations of cAMP in plasma were similar in children with TS (135.4 ± 8.3 pmol/ml) and controls (132.6 ± 7.9 pmol/ml). Postmortem membrane receptor binding for markers within the phosphoinositide (PI) system showed that TS samples had increased [3H]phorbol ester binding to protein kinase C sites in area A17, but normal binding in A4. In contrast, [3H]inositol 1,4,5-triphosphate binding to IP3 receptors showed no significant changes. Our data suggest that alterations in the cAMP and PI second messenger generating systems are not major contributing factors in the development of TS.

Original languageEnglish (US)
Pages (from-to)78-83
Number of pages6
JournalJournal of the Neurological Sciences
Volume128
Issue number1
DOIs
StatePublished - Jan 1995

Keywords

  • Adenylyl cyclase
  • Cyclic AMP
  • IP
  • Phorbol
  • Phosphodiesterase
  • Phosphoinositide
  • Second messenger
  • Tourette syndrome

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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