D-MYO INOSITOL 1,2,6 TRISPHOSPHATE (ALPHA-TRINOSITOL, PP56) - SELECTIVE ANTAGONIST AT NEUROPEPTIDE-Y (NPY) Y-RECEPTORS OR SELECTIVE INHIBITOR OF PHOSPHATIDYLINOSITOL CELL SIGNALING

1. D-myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an iso mer of the second messenger substance, D myo inositol 1,4,5 trisphosph ate, has an interesting pharmacological profile that includes anti-inf lammatory and analgesic effects and antagonism of neuropeptide Y (NPY) -mediated cellular responses. 2. However, not all responses elicited b y this neuropeptide are sensitive to antagonism by pp56. Evidence is e merging, at least in certain tissues, that other receptor populations, in addition to those for NPY, are also sensitive to inhibition by pp5 6. 3. A direct or allosteric interaction of pp56 at receptors for NPY is now considered unlikely and it is more probable that pp56 might int erfere at some point in the phosphatidylinositol signaling pathway, po ssibly at the level of the plasmalemmal inositol 1,3,4,5, tetrakisphos phate receptor. 4. Full realization of the therapeutic potential of th is novel compound, however, must await a thorough characterization of the cellular mechanism(s) associated with the various pharmacological effects of pp56, (C) 1998 Elsevier Science Inc.