Diadenosine polyphosphates as extracellular signal molecules

Dinucleoside polyphosphates are an interesting group of signalling molecule s that control numerous physiological functions. Diadenosine compounds, wit h a backbone of anything from two to seven phosphates, are known to occur n aturally Some of them have been isolated from cerebral nerve terminals and, acting via nucleoside (P1), nucleotide (P2), or dinucleotide receptors, ca n affect central nervous system function. Many of them have been isolated f rom human blood platelet secretory granules acid are potentially involved i n haemostatic mechanisms and peripheral control of vascular tone. Many visc eral organs respond to the application of adenine dinucleotides and, althou gh they act on receptors in the periphery that can be mainly defined as eit her P1 or P2, evidence is now accumulating for discrete dinucleotide recept ors. In the periphery adenine dinucleotides can be potent agonists, with di verse functions, causing contraction or relaxation of smooth muscle. Many P 2X receptor proteins and P2Y receptors have been cloned and adenine dinucle otides have a variable pharmacological profile at these receptors and may b e useful tools for characterising subtypes of P2X and P2Y receptors. This r eview provides a broad description of the many extracellular roles of diade nosine polyphosphates as emerging, yet increasingly important, natural liga nds for a plethora of structurally diverse mononucleotide and dinucleotide receptors. Drug Dev. Res. 52:260-273, 2001. (C) 2001 Wiley-Liss, Inc.