A saturable receptor for ³²P-inositol-l,4,5-trisphosphate in hepatocytes and neutrophils

Several receptors for neurotransmitters, hormones and growth factors cause accelerated phosphodiesteratic breakdown of poly-phosphoinositides when activated^1,2. One of the soluble products of this reaction, inositol-1,4,5-trisphosphate (Ins(l,4,5)P₃) is thought to act as a second messenger signalling the release of Ca²⁺ from intracellular stores³. In support of this hypothesis, several studies have shown that Ins(l,4,5)P₃ releases sequestered Ca²⁺ from permeable cells^4-6 and microsomes⁷⁺⁹. On the basis of certain structural requirements for Ca²⁺-releasing activity by inositol phosphates, it has been postulated that Ins(l,4,5)P₃ acts by binding to a specific intracellular receptor, probably on a component of the endoplasmic reticulum¹⁰. Here we report that ³²P-Ins(l,4,5)P ₃ binds to a specific saturable site in permeabilized guinea pig hepatocytes and rabbit neutrophils, and that the properties of this binding site suggest that it is the physiological receptor for Ins(l,4,5)P₃.