Mechanisms of Intracellular Calcium Movement Activated by Guanine Nucleotides and Inositol-1,4,5-Trisphosphate

Abstract

It is now well established that the intracellular second messenger inositol-1,4,5-trisphosphate (IP₃) is involved in the release of Ca²⁺ from a Ca²⁺ -sequestering organelle, widely considered to be the endoplasmic reticulum (ER) (Berridge and Irvine, 1984; Gill, 1985; Majeruset al., 1986). In a series of recent studies, we observed that a highly sensitive and specific guanine nucleotide regulatory process induces a release of Ca²⁺ in cells that appears very similar to that mediated by IP₃(Gillet al., 1986; Uedaet al., 1986; Chueh and Gill, 1986). Our initial studies were conducted using either permeabilized cells or isolated microsomal membrane vesicles derived from the NIE-115 neuronal cell line; GTP-dependent Ca²⁺ release was observed to be very similar in the two preparations (Gillet al., 1986; Uedaet al., 1986). Recent studies (Henne and Söling, 1986; Jean and Klee, 1986; Chuehet al., 1987) have extended the number of diverse cell types in which the same GTP-activated Ca²⁺ release process is observed. In each cell type, submicromolar GTP concentrations rapidly effect a substantial release of Ca²⁺ sequestered via internal Ca²⁺ -pumping activity within a nonmitochondrial organelle, believed to be the ER. The Ca²⁺ -accumulating properties of this intracellular organelle have been described in detail in earlier studies with permeabilized cells (Gill and Chueh, 1985).