The FP prostanoid receptor: Isoforms and functional studies

Abstract

Prostaglandin F₂(α) (PGF₂(α)) is a locally acting hormone derived from arachidonic acid that is involved in a diverse range of physiological functions including regulation of the corpus luteum and regulation of intraocular pressure. The goal of this research has been to characterize the signaling pathways activated by PGF₂(α). A receptor for PGF₂(α), the FP receptor, had been cloned from a number of species. Based on the cloning of other prostanoid receptors, we hypothesized that isoforms, or alternative splice variants of the FP receptor that differed in their functional coupling might exist. Using a corpus luteum library, we cloned a novel, truncated form of the FP prostanoid receptor, known as the FP(B) receptor isoform. To examine differences in signaling between the FP receptor isoforms, we have generated stable cell lines that express the original FP receptor, known as the FP(A) isoform and cells that express the FP(B) isoform. To date, no differences in the functional coupling between the receptor isoforms have been found. However, during the second messenger studies, we discovered that activation of either receptor isoform leads to changes in the cell morphology and in the cell cytoskeleton. Thus, treatment of the stable cell lines with PGF₂(α) leads to the retraction of cellular projections, and the boundaries between the cells appear less distinct. There is concomitant formation of actin stress fibers and increased tyrosine phosphorylation of p125 FAK. Understanding the molecular mechanisms underlying the PGF₂(α) induced changes in the cell morphology and in the cell cytoskeleton may be relevant for developing better treatments for glaucoma and other diseases.