D-myo inositol 1,2,6, triphosphate (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 isomer of the second messenger substance, D-myo inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes anti-inflammatory and analgesic effects and antagonism of neuropeptide Y (NPY)-mediated cellular responses. 2. However, not all responses elicited by this neuropeptide are sensitive to antagonism by pp56. Evidence is emerging, at least in certain tissues, that other receptor populations, in addition to those for NPY, are also sensitive to inhibition by pp56. 3. A direct or allosteric interaction of pp56 at receptors for NPY is now considered unlikely and it is more probable that pp56 might interfere at some point in the phosphatidylinositol signaling pathway, possibly at the level of the plasmalemmal inositol 1,3,4,5, tetrakisphosphate receptor. 4. Full realization of the therapeutic potential of this novel compound, however, must await a thorough characterization of the cellular mechanism(s) associated with the various pharmacological effects of pp56.
Bell
D
D
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Northern Ireland, UK. d.bell@qub.ac.uk
McDermott
B J
BJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002468:Cell Physiological Phenomena / Q000187:drug effects; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology; D010716:Phosphatidylinositols / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D017476:Receptors, Neuropeptide Y; C059368:atrinositol