An isoform of the sheep prostaglandin receptor has recently been cloned from a day 10 ovine corpus luteum cDNA library. This isoform, or splice variant, is identical to the previously cloned FP receptor throughout the seven transmembrane domains. Nine amino acids into the carboxy tail, the sequence diverges. The original FP receptor, the FPA receptor, continues for 46 amino acids before the termination codon, while the splice variant, the FPB receptor, terminates after only one amino acid. In the divergent region, the FPA receptor contains eleven serines and threonines which are potential phosphorylation sites while the FPB receptor contains none. Radioligand binding competition studies of COS cells transiently transfected with either the FPA or FPB receptor were indistinguishable. We, therefore, hypothesized that the differences in the carboxy tail might lead to differences in the functional properties of the receptor. Traditionally, the FP receptor couples to phosphatidylinositol hydrolysis with a corresponding increase in Ca2+. Prostaglandin F2a (PGF2a) treatment of Xenopus oocytes expressing the FPA receptor leads to a transient inward Cl" current at concentrations as low as 108 M PGF2a. However, PGF2a treatment of oocytes injected with cRNA for the FPB receptor failed to elicit a Cl" current at concentrations of PGF2a up to 10~6 M. To confirm that the oocytes were capable of expressing protein, the cRNA for the Shaker potassium channel was co-injected with the cRNA for the FPA or FPB receptor, and the resulting K+ current measured. The differences in functional coupling between the isoforms is similar to the differences seen between isoforms of another prostaglandin receptor, the EP3 receptor.
|Original language||English (US)|
|Number of pages||1|
|Journal||Proceedings of the Western Pharmacology Society|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas