Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.
An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.
Adham
N
N
Synaptic Pharmaceutical Corporation, Paramus, NJ 07652.
Kao
H T
HT
Schecter
L E
LE
Bard
J
J
Olsen
M
M
Urquhart
D
D
Durkin
M
M
Hartig
P R
PR
Weinshank
R L
RL
Branchek
T A
TA
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015723:Gene Library; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008214:Lymphocytes; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000302:isolation & purification; D011985:Receptors, Serotonin / Q000145:classification / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D014018:Tissue Distribution
D000067956:Adenylyl Cyclase Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D005576:Colforsin; D012701:Serotonin; D013134:Spiperone; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D000262:Adenylyl Cyclases