INOSITOLPOLYPHOSPHATE BINDING-SITES AND THEIR LIKELY ROLE IN CALCIUM REGULATION IN SMOOTH-MUSCLE

Inositol 1,4,5-trisphosphate (InsP(3)) and inositol 1,3,4,5-tetrakisph osphate (InsP(4)) binding sites have been identified in smooth muscle and other tissues. Subcellular localization of these receptors in smoo th muscle indicates that they are present in both the sarcoplasmic ret iculum membrane and the plasma membrane, although the InsP(3) receptor appears predominantly localized in the sarcoplasmic reticulum membran e. The heterogeneity of InsP(3) binding sites is confirmed by radiolig and binding and molecular cloning studies. It is now clear that InsP(3 ), in addition to releasing intracellular Ca2+, can also stimulate Ca2 + entry across the plasma membrane. Although the mechanism of Ca2+ ent ry remains a matter for much debate, what is not in doubt is that incr eases in InsP(3), perhaps acting together with InsP(4), can maintain a constant influx of Ca2+ across the cell membrane. Compared to the Ins P(3) receptor, our understanding of the InsP(4) binding site is limite d. In most cases, including release of intracellular Ca2+ or Ca2+ entr y, the major role of InsP(4) appears to be the potentiation of the Ins P(3)-induced response. Future studies of the InsP(4) binding site by p urification and molecular cloning, as well as subcellular localization , are needed to clarify the role for InsP(4) in the regulation of intr acellular Ca2+.