Molecular Mechanisms of Coupling in Hormone Receptor‐Adenylate Cyclase Systems

Combined Treatment with Citalopram and Buspirone: Effects on Serotonin 5-HT2Aand 5-HT2CReceptors in the Rat Brain

“…Repeated administration of buspirone alone decreased K d , i. e., increased the affinity of [ 3 H]mesulergine for the 5-HT 2C receptors. Because mesulergine is an inverse 5-HT 2C agonist with a higher affinity toward the G protein±uncoupled receptor state [6], our finding indicates that buspirone enhances the conversion of the high-affinity 5-HT 2C receptor±G protein complexes into a low-affinity G protein±uncoupled state [12,58] and thus suppresses the 5-HT 2C receptor-mediated neurotransmission. To our knowledge, this mechanism of action of buspirone has not been previously described.…”

“…Repeated administration of buspirone in combination with citalopram ± but neither of these drugs alone ± decreased both 5-HT 2A receptor agonist and antagonist binding in the frontal cortex, implying a downregulation of this receptor subtype. Even though it is difficult to compare absolute values obtained with 3 H-ligands with that of 125 I-ligands, it seems that the relative proportion of the high-affinity state of the total amount of receptors (i. e., the ratio between agonist and antagonist binding [12,58]) is higher for the 5-HT 2A subtype in rat frontal cortex than, e. g., for the 5-HT 2C receptor subtype in rat choroid plexus (cf. y-axis scales in Fig.…”