Preamble 5HT2C Receptor and Second Messenger Coupling

In most cases, stimulation of the 5-HT2C receptor excites neurons. Indeed, stimulation of the 5-HT2C receptor enhances phosphoinositol turnover via Gq-protein coupling and activation of phospholipase C (Conn et al. 1986; Berg et al. 1998). This effect leads to a marked increase in intracellular Ca2+ (Julius et al. 1988).

In addition, the 5-HT2C receptor has been functionally linked to guanylyl cyclase in the porcine choroid plexus (Hartig et al. 1990) and its stimulation increases cyclic guanosine monophosphate (GMP) formation (Kaufman et al. 1995). The receptor may also couple to phosplipase A2 or a Gi protein when expressed in heterologous cell lines (Berg et al. 2001). More recently, a calmodulin-beta-arrestin pathway, independent from G proteins, has been reported (Berg et al. 2008; Labasque et al. 2008). Interestingly, in most cases, the 5-HT2C receptor appears constitutively active in heterologous systems. For example, 5-HT2C receptor activates phospho-inositol hydrolysis in the absence of agonists when expressed in NIH-3T3 fibro-blasts (Westphal et al. 1995) and could contribute to the basal activity of cells in the choroid plexus (Barker et al. 1994) and basal ganglia (De Deurwaerdere et al. 2004). In line with these data, several studies have shown that 5-HT2C receptors display a high propensity to couple to Gq protein. This property could account for the functional difference in the response of 5-HT2A and 5-HT2C receptors to 5-HT. Indeed, the ability of 5-HT2C receptors to stimulate phosphoinositol turnover is tenfold greater than that of 5-HT2A receptors (Leonhardt et al. 1992). This difference has been observed in native rat striatal tissue, despite the four times lower expression of 5-HT2C receptors compared with 5-HT2A receptors in this region (Wolf and Schutz 1997). Yet, the higher coupling of 5-HT2C receptors to intracellular pathways is critically dependent on the isoforms that result from the editing process. Indeed, editing dramatically lowers the coupling efficiency compared with the nonedited form of the receptor (Berg et al. 2001). This molecular mechanism is probably an important component of 5-HT2C receptor-dependent transmission in the brain, including in the basal ganglia. As discussed earlier, studies are still necessary to determine the distribution of the different isoforms of the receptor in these regions.

Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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