| Positron emission tomographic (PET) imaging of receptors in the living human brain shows promise for understanding the role of receptors in human health and disease. Towards this end, a potential imaging agent for serotonin 5-HT{dollar}sb2{dollar} receptors was developed. N1-methyl-2-{dollar}sp{lcub}125{rcub}{dollar}I-lysergic acid diethylamide ({dollar}sp{lcub}125{rcub}{dollar}I-MIL) exhibited increased affinity and selectivity for 5-HT{dollar}sb2{dollar} receptors in rodent brain. In vivo binding studies in mice indicated that {dollar}sp{lcub}125{rcub}{dollar}I-MIL labeled serotonin receptors with the highest frontal cortex to cerebellum ratio, making it a promising ligand for both in vitro and in vivo labeling of serotonin receptors in the mammalian brain.; Recently, the 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} site serotonergic binding site was described as having high densities in the mammalian choroid plexus. We have shown that the serotonin 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} site is a functional receptor in both rat and pig, activating phosphoinositide hydrolysis in choroid plexus. The pharmacology of this choroid plexus response is distinct from that for 5-HT-stimulated phosphoinositide hydrolysis in cerebral cortex, where the response is mediated by the serotonin 5-HT{dollar}sb2{dollar} receptor. A disparity in response size between rat and pig was detected and was due, in part, to differences in incorporation of {dollar}sp3{dollar}H-myo-inositol into phospholipids, but also may reflect differences in receptor-effector coupling.; In mRNA-injected Xenopus oocytes, the 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} receptor couples to phosphoinositide hydrolysis and elicits a Ca{dollar}sp{lcub}2+{rcub}{dollar}-dependent chloride conductance increase. A strategy was developed for cloning neurotransmitter and ion-channel cDNAs using such an electrophysiological assay. With this strategy, a cDNA for the serotonin 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} receptor was isolated. The 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} receptor has a single subunit encoded by a 5-kilobase RNA. Based on the deduced amino acid sequence, the 5-HT{dollar}sb{lcub}1rm C{rcub}{dollar} receptor has seven membrane spanning regions like adrenergic and muscarinic receptors, with an additional hydrophobic region which may serve as a signal peptide. Unlike the adrenergic and muscarinic receptors, however, this serotonin receptor gene contains at least three introns in the protein coding region. Evidence is presented which suggests a loss of splicing specificity in choroid plexus tumors. |
