Pharmacological Characterization of an FP Prostaglandin Receptor on Rat Vascular Smooth Muscle Cells (A7r5) Coupled to Phosphoinositide Turnover and Intracellular Calcium Mobilization

• Published in: The Journal of pharmacology and experimental therapeutics 1998-07, Vol.286 (1), p.411-418
• Main Authors: Griffin, B W, Magnino, P E, Pang, I H, Sharif, N A
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Cells, Cultured; Estrenes - pharmacology; Muscle, Smooth, Vascular - metabolism; Phosphatidylinositols - metabolism; Prostaglandins F, Synthetic - pharmacology; Pyrrolidinones - pharmacology; Rats; Receptors, Prostaglandin - physiology
• ISSN: 0022-3565; 1521-0103

An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line has been characterized by assays of phosphoinositide (PI) turnover and intracellular calcium mobilization stimulated by structurally diverse PGs. In the PI turnover assay, cloprostenol was the most potent PG tested, with a potency (EC 50 ) of 0.84 ± 0.06 nM (mean ± S.E.M., n = 34), and was a full agonist. Other known FP receptor agonists tested in this assay had efficacies ≥85% of the cloprostenol value and high potencies: 16-phenoxy PGF 2α (2.05 ± 0.19 nM), 17-phenyl PGF 2α (2.80 ± 0.59 nM), fluprostenol (4.45 ± 0.19 nM), PGF 2α (30.9 ± 2.82 nM) and PhXA85 (43.5 ± 11.4 nM). Other classes of PGs evaluated (PGD 2 , enprostil, 17-phenyl PGE 2 , PGE 2 , sulprostone and U-46619) were less potent and less efficacious than the FP receptor agonists, or were inactive. For a large group of standard PGs evaluated in the PI turnover assay, both potencies and efficacies correlated well with those reported for the FP receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF 2α as stimuli of intracellular calcium mobilization matched well their potencies in the PI turnover assay, but fluprostenol had twice the efficacy of PGF 2α . Both signaling responses stimulated by fluprostenol were significantly inhibited by U73122, a selective inhibitor of phosphoinositide turnover (IC 50 = 1.25 ± 0.16 μM for PI turnover), and by chelation of calcium in the medium. Together with the PI turnover data, these studies of intracellular calcium mobilization linked to activation of the FP receptor, provide additional characterization of the pharmacological properties of this receptor.