Cloning and expression of a cDNA for the human prostanoid FP receptor.
A cDNA clone coding for a functional human prostanoid FP receptor has been isolated from a uterus cDNA library. The human FP receptor consists of 359 amino acid residues with a predicted molecular mass of 40,060, and has the seven putative transmembrane domains characteristic of G-protein-coupled receptors. Challenge of Xenopus oocytes expressing the FP receptor with 10 nM of either prostaglandin (PG) F2 alpha or the selective FP-receptor agonist fluprostenol resulted in an elevation in intracellular Ca2+. Radioreceptor binding studies using membranes prepared from mammalian COS cells transfected with the FP receptor cDNA showed that the rank order of potency for prostaglandins and prostaglandin analogs in competition for [3H]PGF2 alpha specific binding sites was as predicted for the FP receptor, with PGF2 alpha approximately fluprostenol > PGD2 > PGE2 > U46619 > iloprost. In summary, we have cloned the human prostanoid FP receptor which is functionally coupled to the Ca2+ signalling pathway.
Abramovitz
M
M
Department of Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Boie
Y
Y
Nguyen
T
T
Rushmore
T H
TH
Bayne
M A
MA
Metters
K M
KM
Slipetz
D M
DM
Grygorczyk
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016376:Oligonucleotides, Antisense; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011869:Radioligand Assay; D011982:Receptors, Prostaglandin / Q000096:biosynthesis* / Q000737:chemistry / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014316:Tritium; D014599:Uterus / Q000378:metabolism*; D014982:Xenopus laevis
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D014316:Tritium; C006326:fluprostenol; D015237:Dinoprost; D002118:Calcium