FP PROSTANOID ISOFORMS &CALCIUM SIGNALING IN THE EYE

University Of California San Diego, La Jolla CA

Investigators

Abstract

DESCRIPTION (Verbatim from applicant's abstract): The endogenous prostaglandin PGF2-alpha exerts a broad range of biological effects through the interaction with plasma membrane-bound FPA and FPB receptors that are coupled to the Gq/G11 guanine nucleotide-binding protein (G protein). The FPB receptor isoform is generated from the utilization of a splice site and the loss of a 3.2 kb intron in the FP receptor gene. This alternative splicing produces a truncation of the carboxyl tail and the loss of 46 amino acids. Activation of both receptor isoforms stimulates the accumulation of inositol 1,4,5-trisphosphate (IP3) with equivalent efficacy, but differs at the level of Ca2+ mobilization. The mechanism and functional significance of the difference in Ca2+ signaling is not known and is the focus of this proposal. Specific aim 1 will examine the functional difference in Ca2+ mobilization between the two receptor isoforms by monitoring the Ca2+-activated Cl- channels in Xenopus oocytes. Specific aim 2 will clone the human FPB prostanoid isoform and develop subytype-specific antibodies to determine the ocular distribution of these receptor isoforms. Understanding the cellular components involved in the Ca2+ signaling and the tissue distribution of the FP prostanoid receptor isoforms are necessary steps towards understanding PGF2-alpha's hypotensive actions in the eye.