A NOVEL RAT SEROTONIN RECEPTOR - PRIMARY STRUCTURE, PHARMACOLOGY, ANDEXPRESSION PATTERN IN DISTINCT BRAIN-REGIONS

Serotonin mediates various central and peripheral functions by its abi lity to bind to and activate a variety of receptors that belong to fou r pharmacologically defined classes termed 5-HT1 to 5-HT4. Using a pol ymerase chain reaction-derived probe, a clone, GPRFO, was isolated fro m a rat brain cDNA library. This cDNA encodes a putative G protein-cou pled receptor that exhibits highest similarity to receptors for biogen ic amines. RNA blot analysis indicated that the corresponding gene is expressed in the diencephalon. Consistent with the RNA blot data, GPRF O mRNA has been detected by in situ hybridization in the centrolateral , central medial, and intermediodorsal thalamic nuclei. Highest amount s of GPRFO mRNA, however, have been observed in a small area, i.e., th e hippocampal rudiments and the stria longitudinalis. COS-7 cells tran siently transfected with the GPRFO cDNA acquire saturable high-affinit y binding sites for [H-3]serotonin (K(D) = 41 nM). The pharmacological properties of the receptor differ from those of the known serotonin r eceptor subtypes, suggesting that the GPRFO cDNA encodes a novel serot onin receptor that is expressed in distinct rat brain regions.