The extraction, isolation and purification of an endogenous regulator for the 5-HT2 receptor

Early studies indicated that serotonin, a primary transmitter in the central nervous system, may not represent the primary endogenous regulator for the 5-HT2 receptor labeled by [3H]-ketanserin. Instead, an endogenous ligand may be responsible for modulating the [3H]-ketanserin site. Through different isolation and purification procedures, a pronase-sensitive peptide with activity on [3H]-ketanserin binding was identified in the rat brain. This peptide seems specific for the 5-HT2 receptor since it does not displace the binding of [3H]-imipramine or [3H]-mianserin from rat cortical membranes and is able to stimulate PI turnover in a ketanserin sensitive fashion. Given the role of 5-HT2 receptors in the action of antidepressants, this finding may help understand some of the molecular mechanisms involved in antidepressant effect.