Formation and actions of inositol phosphates

A wide variety of hormone and neurotransmitter receptors mediate control of cell function through activation of a phosphodiesteratic breakdown of polyphosphoinositides. In electrically permeabilized pancreatic acinar cells, non-hydrolyzable derivatives of GTP can activate this phosphodiesterase, and potentiate the action of hormones. This suggests receptor coupling to the enzyme probably involves a guanine nucleotide-dependent regulatory protein analogous to the ones involved in regulating adenylate cyclase. The water-soluble product of this reaction inositol-1,4,5-tris-phosphate ((1,4,5)IP/sub 3/), signals Ca/sup 2 +/ release from a fraction of the endoplasmic reticulum which, in the liver, constitutes about 40% of the non-mitochondrial Ca/sup 2 +/ accumulating activity. By using a high specific activity /sup 32/P-labelled (1,4,5)IP/sub 3/, a specific and saturable binding site for (1,4,5)IP/sub 3/ can be demonstrated. Binding of (1,4,5)IP/sub 3/ and (2,4,5)IP/sub 3/ to this site is well correlated with the Ca/sup 2 +/-releasing actions of these molecules. This may indicate that the actions of (1,4,5)IP/sub 3/ are mediated by a specific receptor on the endo- plasmic reticulum. The emptying of the sensitive Ca/sup 2 +/-pool in the endoplasmic reticulum by (1,4,5)IP/sub 3/ may secondarily signal the influx of Ca/sup 2 +/ from the extracellular space.