The Serotonin 5‐HT2C Receptor Is a Prominent Serotonin Receptor in Basal Ganglia: Evidence from Functional Studies on Serotonin‐Mediated Phosphoinositide Hydrolysis

• Published in: Journal of neurochemistry Vol. 69; no. 4; pp. 1449 - 1458
• Main Authors: Wolf, William A., Schutz, Laurence J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.1997; Blackwell
• Subjects: Animals; Basal Ganglia - metabolism; Binding Sites; Biological and medical sciences; Brain; Brain - enzymology; Calcium - pharmacology; Caudate Nucleus - enzymology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Frontal Lobe - enzymology; Fundamental and applied biological sciences. Psychology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Hydrolysis; Male; Phosphatidylinositols - metabolism; Phospholinositide hydrolysis; Phospholipase C; Rat; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - metabolism; Serotonin - pharmacology; Serotonin - physiology; Serotonin receptor; Type C Phospholipases - metabolism; Vertebrates: nervous system and sense organs; Phosphoinositide; Rat; Enzyme; Rodentia; Central nervous system; 5-HT2 receptor; Esterases; Basal ganglion; Binding site; Phosphoric diester hydrolases; In vitro; Phospholipase C; Signal transduction; Vertebrata; Mammalia; Caudate nucleus; Hydrolases; Subtype; Brain (vertebrata)
• DOI: 10.1046/j.1471-4159.1997.69041449.x
• ISSN: 0022-3042

: 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 GTPγS (1 µM), 5‐HT increased PLC activity in caudate membranes. Pharmacological analysis using the selective 5‐HT2A antagonist, spiperone, and the nonselective 5‐HT2A/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.