The rat 5-hydroxytryptamine1B receptor is the species homologue of the human 5-hydroxytryptamine1D beta receptor.
The relationship between the serotonin 5-hydroxytryptamine1B (5-HT1B) and 5-HT1D receptors has been the topic of much investigation and speculation since their complementary species distribution was first appreciated. The cloning of genes encoding 5-HT1D receptors has provided tools to investigate this relationship directly. In this study, a rat gene has been cloned that encodes the rat 5-HT1B receptor. Evaluation of the structure of this gene shows that it is a member of the guanine nucleotide-binding protein-coupled receptor superfamily. Comparison of the amino acid sequence of the rat gene with the human 5-HT1D beta gene showed a 93% overall identity and a 96% identity in the transmembrane regions. Comparison of the two sequences revealed zero to two amino acid changes in each of these transmembrane regions, as well as a striking conservation in the connecting loops, indicative of the relationship expected for species homologues of the same gene. The rat gene was expressed transiently in COS-7 cells, and membranes derived from these cells were shown to bind [125I]iodocyanopindolol. The pharmacological profile of this binding site closely matched that of the native rat 5-HT1B receptor (r = 0.95) but not the 5-HT1D receptor (r = 0.07). The cloned rat 5-HT1B receptor was found to couple to the inhibition of adenylate cyclase activity, as expected for a 5-HT1B receptor. These data indicate that, although the 5-HT1B and 5-HT1D receptors are pharmacologically distinct, they are species variants of the same receptor gene, the 5-HT1D beta gene.
Adham
N
N
Neurogenetic Corporation, Paramus, New Jersey 07652.
Romanienko
P
P
Hartig
P
P
Weinshank
R L
RL
Branchek
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D003001:Cloning, Molecular; D006801:Humans; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008969:Molecular Sequence Data; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; D020120:Iodocyanopindolol; D010869:Pindolol