The serotonin 5-HT2C receptor is a prominent serotonin receptor in basal ganglia: evidence from functional studies on serotonin-mediated phosphoinositide hydrolysis.
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.
Wolf
W A
WA
Biological Psychiatry and Research Service, Hines VA Medical Center, Illinois 60141, U.S.A.
Schutz
L J
LJ
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology; D002421:Caudate Nucleus / Q000201:enzymology; D005625:Frontal Lobe / Q000201:enzymology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006868:Hydrolysis; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010738:Type C Phospholipases; D002118:Calcium