Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype.
A functional cDNA clone coding for the human prostaglandin E receptor EP1 subtype has been isolated from a human erythroleukemia cell cDNA library probed by low-stringency hybridization using a polymerase chain reaction fragment of the human thromboxane receptor. The human EP1 receptor is comprised of 402 amino acids with a predicted molecular mass of 41,858 and has the topography common to all G-protein-coupled receptors with seven predicted transmembrane spanning domains. Prostaglandin (PG) E2 challenge of Xenopus oocytes injected with EP1 cDNA resulted in an increase in intracellular Ca2+. In addition, the rank order of potency for prostaglandins in competition for [3H]PGE2 specific binding to membranes prepared from EP1 cDNA transfected COS cells was PGE2 > PGE1 > PGF2 alpha > PGD2. Furthermore, the EP1 receptor-selective antagonists AH 6809 and SC19220 were more potent than the EP2 receptor-selective agonist butaprost in these competition binding assays. In summary, therefore, we have cloned the human EP1 receptor subtype which is functionally coupled to an increase in intracellular Ca2+.
Funk
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Division of Clinical Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-6602.
Furci
L
L
FitzGerald
G A
GA
Grygorczyk
R
R
Rochette
C
C
Bayne
M A
MA
Abramovitz
M
M
Adam
M
M
Metters
K M
KM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D018078:Receptors, Prostaglandin E / Q000235:genetics*; D017482:Receptors, Thromboxane / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014981:Xenopus
D018076:DNA, Complementary; D018078:Receptors, Prostaglandin E; D017482:Receptors, Thromboxane; D015232:Dinoprostone