Second messenger systems in Tourette's syndrome.
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 GTP gamma S (a non-hydrolyzable GTP analog), forskolin (a selective enzyme stimulator), or (-)-isoproterenol (a beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Singer
H S
HS
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-8811, USA.
Dickson
J
J
Martinie
D
D
Levine
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D002648:Child; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D005879:Tourette Syndrome / Q000378:metabolism* / Q000473:pathology
D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D011943:Receptors, Adrenergic, beta; D017448:Receptors, Dopamine D2; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases