Action of Natural Products on P2 Receptors: A Reinvented Era for Drug Discovery

Abstract

Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2) receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines.

P2X7‐dependent, but differentially regulated release of IL‐6, CCL2, and TNF‐α in cultured mouse microglia

“…3), indicating that P2X7 activation leads to IL-6 and CCL2 release in microglia. P2X4 allosteric potentiator ivermectin at 3 lM was used in combination with 50 mM of ATP (Faria, 2012), as it was shown that ivermectin can enhance the P2X4 effects by stabilizing the ATP-induced open state (Bernier, 2008). 3B).…”

“…Among these cytokines, only CCL2 and TNF-a release was up-regulated by 1 mM ATP (CCL2vehicle 532.32 6 67.28 pg/mL, 1 mM ATP 770. P2X4 allosteric potentiator ivermectin at 3 lM was used in combination with 50 mM of ATP (Faria, 2012), as it was shown that ivermectin can enhance the P2X4 effects by stabilizing the ATP-induced open state (Bernier, 2008). However, ivermectin and ATP cotreatment did not induce the release of IL-6, CCL2, and TNF-a in cultured microglia FIGURE 3: Pharmacological characterization of the BzATP-dependent effects on cytokine release in cultured microglia.…”

Increased Expression of P2RY2, CD248 and EphB1 in Gastric Cancers from Chilean Patients

“…After the validation process, we determined that 3 of them had high levels of sensitivity for the disease detection. P2RY2 belongs to the family of purynergic receptors coupled to G protein, of which P2Y4, P2Y6 and P2Y11 (Faria et al, 2012). P2Y2 receptor recognizes ATP and UTP ligands, and bind G-protein by phospholipase C (PLC) activation and mobilizing intracellular Ca 2+ (Li et al, 2011).…”

Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors

“…Natural products have recently been reported as showing antagonistic properties on the P2R receptors [14]. Several of those that were found to be related to analgesic or anti-inflammatory activity on P2XR are presented in Figure 1.…”