We have identified two novel splice variants of the metabotropic gamma-aminobutyric acid receptor (GABA(B)R1), designated GABA(B)R1c and GABA(B)R1d, when screening a rat cerebellum cDNA library. GABA(B)R1c has an amino acid sequence identical to GABA(B)R1b, a member of GABA(B)R1 isoforms, and an additional 93-bp insertion that generates an additional 31-amino-acid sequence in the fifth transmembrane region of GABA,Rlb. Thus, GABA,Rlc may have a structural variation in the second extracellular loop and fifth transmembrane region. GABA(B)R1d also has an amino acid sequence identical to GABA,Rlb and an additional insertion of 566 bp that generates a divergent amino acid sequence in the carboxyl-terminal end. Reverse-transcription polymerase chain reaction analysis showed that in various rat tissues GABA(B)R1c mRNA was ubiquitously expressed and GABA(B)R1d mRNA in forebrain, cerebellum, eye, kidney, and urinary bladder. GABA(B)R1 isoforms may function not only in the central nervous system but also in various peripheral tissues. (C) 1998 Academic Press.