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Cloning and Expression of a 5‐Hydroxytryptamine 7 Receptor Positively Coupled to Adenylyl Cyclase
Author(s) -
Tsou Annping,
Kosaka Alan,
Bach Chinh,
Zuppan Patti,
Yee Calvin,
Tom Leonard,
Alvarez Robert,
Ramsey Scott,
Bonhaus Douglas W.,
Stefanich Eric,
Jakeman Lyn,
Eglen Richard M.,
Chan Hardy W.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63020456.x
Subject(s) - spiperone , biology , adenylyl cyclase , receptor , microbiology and biotechnology , cdna library , 5 ht receptor , agonist , complementary dna , serotonin , biochemistry , gene
A cDNA clone (designated as GP2‐7) encoding a novel 5‐hydroxytryptamine (5‐HT) receptor was isolated from a guinea pig hippocampal library. The receptor shares amino acid homology within the hydrophobic domains with other cloned 5‐HT receptor subtypes (34–48%). The sequence of GP2‐7 is homologous to that described for a novel receptor previously cloned from a rat brain cDNA library and provisionally designated as 5‐HT 7 . mRNA for GP2‐7 was detected in cortical and limbic brain regions. Transiently expressed GP2‐7 showed high‐affinity binding to [ 3 H]5‐HT ( pK i = 9.0) with the following rank order of affinities: 5‐carboxyamidotryptamine (5‐CT) > 5‐HT = 5‐methoxytryptamine (5‐MeOT) > methiothepin > 8‐hydroxy‐2‐(dipropylamino)tetralin (8‐OH‐DPAT) > spiperone ≫ sumatriptan. Adenylyl cyclase activity in CHO‐K1 cells transiently transfected with GP2‐7 was stimulated by several analogues of 5‐HT with the following order of potency: 5‐CT > 5‐HT = 5‐MeOT > dipropyl‐5‐CT > 8‐OH‐DPAT. Methiothepin and spiperone were potent antagonists. Preliminary analysis suggests that GP2‐7 closely resembles a receptor in the guinea pig hippocampus that exhibits a high affinity toward 5‐CT.