Inositol tetrakisphosphate as a second messenger: Confusions, contradictions, and a potential resolution

Abstract

The second messenger function of inositol 1,4,5‐ trisphosphate (InsP₃) is now well‐defined – it mobilizes Ca²⁺ from intracellular stores so that cytosolic Ca²⁺ increases. However, the function of inositol 1,3,4,5‐ tetrakisphosphate (InsP₄) has proved much more difficult to fathom, as it has been reported to exert a wide variety of effects in a collection of experimental systems. In this review, a proposed molecular mechanism for InsP₄ actions is discussed; it is suggested that InsP⁴ is the second messenger that controls Ca²⁺ entry into cells, and that it does so by binding to a receptor which itself interacts, directly or Indirectly, with the receptor for InsP³ It is proposed that this is InsP₄'s true physiological function, but the mechanism by which it exerts this function has led to confusing data concerning its action, and also to some misconceptions about how inositol phosphates control Ca²⁺ entry.