A PCR cloning strategy using primers designed from sequences selective
ly conserved among a cannabinoid receptor and two orphan receptors, wa
s used to isolate novel G protein-coupled receptors. rCNL3, a 1.75 kb
cDNA encoding a 363 amino acid protein, was isolated from a rat cerebr
al cortex library. Sequence analysis showed that rCNL3 possesses a num
ber of structural characteristics of G protein-coupled receptors and h
as 61% amino acid identity (from transmembrane region one through the
carboxyl-terminus) with two other candidate G protein-coupled receptor
s. Therefore, these three receptors may comprise a receptor subfamily
with identical or closely related endogenous ligands. Northern and in
situ hybridization experiments demonstrated that rCNL3 mRNA is express
ed in the rat brain, with a prominent distribution in striatum.