Cultured astrocytes express messenger RNA for multiple serotonin receptor subtypes, without functional coupling of 5-HT 1 receptor subtypes to adenylyl cyclase

Abstract

The literature describing the expression of 5-HT receptor subtypes by astrocytes is controversial and incomplete. It is clear that primary cultures of astrocytes express receptors of the 5-HT 2 family coupled to phospholipase C and of the 5-HT 7 receptor family positively coupled to adenylyl cyclase. Cultured astrocytes have also been reported to express receptors of the 5-HT 1 family, although the exact subtypes present are unknown. In the present study we have investigated which of the known rat G-protein coupled 5-HT receptor mRNAs are expressed by cultured astrocytes. Reverse transcriptase–polymerase chain reaction (RT-PCR) revealed expression of 5-HT 1A, 5-HT 1B, 5-HT 1D, 5-HT 1F, 5-HT 2A, 5-HT 2B, 5-HT 2C, 5-HT 5B, 5-HT 6 and 5-HT 7 receptor mRNAs in astrocytes derived from 2-day old rats and cultured for 10–12 days. Messenger RNAs for 5-HT 4 and 5-HT 5A receptors were not detected. The functional expression of 5-HT 1 receptor subtypes was investigated by measuring the ability of 5-HT 1 receptor agonists: 8-OH-DPAT (5-HT 1A receptors), RU24969 (5-HT 1A, 5-HT 1B, 5-HT 1D, and 5-HT 1F receptors) or sumatriptan (5-HT 1B, 5-HT 1D, and 5-HT 1F receptors) to modulate forskolin or isoproterenol stimulated cAMP production. These compounds, at concentrations up to 10 μM, did not significantly attenuate cAMP production. These results indicate that although astrocytes express mRNA for each of the five 5-HT 1 receptor subtypes which have been isolated from the rat, these receptors are not coupled to the inhibition of adenylyl cyclase.