P1 and P2 receptors in cell growth and differentiation

Besides their well-established roles as short-term neurotransmitters, nucleotides and nucleosides are also potent regulators of cell growth and differentiation. Compelling evidence obtained on neural, immune, cardiovascular and respiratory system cells, as well as on many other cell types, suggests that these compounds may act as physiological regulators of the phenotype, proliferation and apoptosis of target cells, with a potential in both development and maturation, and in tissue repair and remodeling after trauma and ischemia. Studies by several authors have also made clear that the trophic actions of nucleotides and nucleosides may be either direct or mediated by modulation of synthesis and release of secondary trophic substances (e.g., polypeptidic growth factors and cytokines). In many instances, the involvement of specific P1 or P2 receptors has been established, which discloses the possibility of regulating the local production of neurotrophins, pleiotrophis, cytokines and other trophic agents via selective purinoceptor ligands. The pharmacological modulation of these receptors may therefore have a therapeutic potential in various diseases, ranging from cancer and neurodegenerative disorders, to prevention of recurrent stroke and promotion of wound and gastric ulcer healing. Drug Dev. Res. 39:393–406, 1996.