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Cloning, expression and pharmacology of a truncated splice variant of the human 5‐HT 7 receptor (h5‐HT 7(b) )
Author(s) -
Jasper J. R.,
Kosaka A.,
To Z. P.,
Chang D. J.,
Eglen R. M.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701336
Subject(s) - receptor , 5 ht5a receptor , gabbr1 , enzyme linked receptor , alternative splicing , protease activated receptor 2 , g protein coupled receptor , microbiology and biotechnology , splice , hek 293 cells , interleukin 21 receptor , interleukin 5 receptor alpha subunit , biology , chemistry , gene isoform , gene , biochemistry , protein subunit , g alpha subunit
1 The rat 5‐hydroxytryptamine (5‐HT) 7 receptor displays two splice variations, a long form, and a truncated splice isoform, arising from the introduction of a stop codon near the carboxy‐terminus. The human 5‐HT 7 receptor gene contains at least two introns and encodes a 445 amino acid 5‐HT receptor. 2 A truncated splice variation in the human 5‐HT 7 receptor was isolated from a human placental cDNA library. In accordance with current NC‐IUPHAR nomenclature guidelines, it is suggested that this receptor be denoted as the h5‐HT 7(b) receptor and the long form of the receptor as h5‐HT 7(a) . 3 The h5‐HT 7(b) receptor was stably expressed in HEK 293 cells and ligand affinities were determined by displacement of [ 3 H]‐5‐carboxyamidotryptamine (5‐CT; K d =0.28±0.06 n M , B max =7.3±1.7 pmol mg −1 protein). The rank order of affinities (p K i ) for a series of ligands was: 5‐carboxamidotryptamine (5‐CT, 9.65)>5‐hydroxytryptamine (5‐HT, 9.41)>methiothepin (8.87)>mesulergine (7.87)>8‐hydroxy‐2(di‐n‐propylamino)tetralin (8‐OH‐DPAT, 6.85)>ketanserin (6.44). 4 The h5‐HT 7(b) receptor coupled positively to adenylyl cyclase in HEK 293 cells. This response was elicited by a number of agonists with the following order of potency (pEC 50 ): 5‐CT (8.7±0.11)>5‐MeOT (5‐methoxytryptamine; 8.1±0.20)>5‐HT (7.5±0.13)>tryptamine (5.6±0.36)>8‐OH‐DPAT (5.3±0.28)>5‐methoxytryptamine (5.0±0.06). This rank order was comparable to that observed in the radioligand binding studies. 5 In a similar fashion to that described for the 5‐HT 7(a) receptor, PCR studies suggested that the 5‐HT 7(b) receptor mRNA is found in great abundance throughout the brain, in the small intestine and aorta. 6 It is concluded that the h5‐HT 7 receptor, like the rat receptor, exists as splice variants exhibiting similar pharmacology, signal transduction and distribution. It is thus likely that there exists a complex physiological role for alternate splicing products of the 5‐HT 7 receptor gene.British Journal of Pharmacology (1997) 122 , 126–132; doi: 10.1038/sj.bjp.0701336