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  • Title: The serotonin 5-HT2C receptor is a prominent serotonin receptor in basal ganglia: evidence from functional studies on serotonin-mediated phosphoinositide hydrolysis.
    Author: Wolf WA, Schutz LJ.
    Journal: J Neurochem; 1997 Oct; 69(4):1449-58. PubMed ID: 9326273.
    Abstract:
    Serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A and 5-HT2C receptors belong to the class of phosphoinositide-specific phospholipase C (PLC)-linked receptors. Conditions were established for measuring 5-HT2A-linked and 5-HT2C-linked PLC activity in membranes prepared from previously frozen rat frontal cortex and caudate. In the presence of Ca2+ (300 nM) and GTPgammaS (1 microM), 5-HT increased PLC activity in caudate membranes. Pharmacological analysis using the selective 5-HT2A antagonist, spiperone, and the nonselective 5-HT(2A/2C) antagonist, mianserin, demonstrated that over half of the 5-HT-stimulated PLC activity was due to stimulation of 5-HT2C receptors as opposed to 5-HT2A receptors. Radioligand binding assays with [3H]RP 62203 and [3H]mesulergine were used to quantify 5-HT2A and 5-HT2C sites, respectively, in caudate. From these data, the Bmax for caudate 5-HT2A sites and 5-HT2C sites was 165.4 +/- 9.7 fmol/mg of protein and 49.7 +/- 3.3 fmol/mg of protein, respectively. In contrast to that in caudate, PLC activity in frontal cortex was stimulated by 5-HT in a manner that was inhibited by the 5-HT2A-selective antagonists, spiperone and ketanserin. Taken together, the results indicate that 5-HT2A- and 5-HT2C-linked PLC activity can be discerned in brain regions possessing both receptor subtypes using membranes prepared from previously frozen tissue. More importantly, significant 5-HT2C-mediated phosphoinositide hydrolysis was observed in caudate, despite the relatively low density of 5-HT2C sites. The significance of these observations with respect to the physiological function of 5-HT2C receptors is discussed.
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