COEXPRESSION IN VERTEBRATE TISSUES AND CELL-LINES OF MULTIPLE INOSITOL 1,4,5-TRISPHOSPHATE (INSP(3)) RECEPTORS WITH DISTINCT AFFINITIES FORINSP(3)

Inositol 1,4,5-trisphosphate (InsP(3)) is a ubiquitous second messenge r in eukaryotic cells that triggers Ca2+ release from intracellular st ores. Three types of InsP(3) receptors have been identified in mammals . The three receptor types are encoded by homologous genes and are str ucturally similar, suggesting two alternative hypotheses about the bio logical significance of multiple InsP(3) receptors: (a) the different InsP(3) receptors could have similar functions as InsP(3)-gated Ca2+ c hannels, and the presence of multiple genes could then serve as a mech anism to allow tissue-specific differential expression of receptors; o r (b) the different receptors are coexpressed in cells but have distin ct biological roles in these cells. To test these hypotheses, we have investigated the similarities and differences between the expression, alternative splicing, and ligand binding of different receptors. Our r esults demonstrate co-expression of different InsP(3) receptors in alm ost all tissues and cell lines tested. Although all receptor types exh ibit a similar specificity for inositol phosphates, the different rece ptors have different affinities for InsP(3), with a relative order of affinities of type II > type I > type III. These findings suggest that the presence of multiple InsP(3)-sensitive Ca2+ pools with differenti al responsiveness to InsP(3) may be a general property of all cells me diated by the presence of multiple types of InsP(3) receptors.