Pharmacological Characterization of the Prostanoid FP-Receptor

Investigation of contractile responses of the cat iris sphincter and rat colon and the calcium signal in Swiss 3T3 cells gave the following rank order of potency for natural and synthetic prostanoids in all three preparations: fluprostenol ≥ prostaglandin F2α (PGF2α) > PGD2 > PGE2 > U-46619 > PGI2 > BW245C (=0) with the exception of the rat colon where the rank order for PGD2 and PGE2 was reversed. PGI2 was inactive in Swiss 3T3 cells. These findings indicate that the responses were mediated by a prostanoid FP-receptor. Contractions of cat iris and rat colon induced with fluprostenol or PGF2α were totally dependent on extracellular calcium. Further investigations in the cat iris demonstrated that prostanoid-induced calcium influx occurs through receptor-operated channels. Contractions could be blocked with La3+ or Mn2+, but were unaffected by diltiazem or verapamil. The increase in cytosolic calcium in Swiss 3T3 cells, on the other hand, was mainly derived from intracellular stores. These studies suggest that smooth muscle and mouse fibroblasts utilize different calcium pools upon FP-receptor stimulation.