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Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
ATP has now also established its role as a transmitter through its widespread receptor-mediated actions in the body. ATP binds with two types of receptors, P2X and P2Y receptors. P2X receptors are ligand-gated ion channel receptors subdivided into seven subtypes (P2X1 to P2X7). P2X receptors are widely distributed all over the body. P2X1 and P2X2 receptors are found in the dorsal horn, and hence play an important role in sensory transmission. P2Y receptors are GPCRs and there are eight subtypes of P2Y receptors such as P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14 (Rang et al., 2011; Edward and Gibb, 1993; Barrett et al., 2009; Webster, 2001).
Regulation of microglial physiology by the microbiota
Published in Gut Microbes, 2022
Adult microglia exhibit several marked adaptations to their role as the primary immunocompetent cells of the brain. Firstly, their unique transcriptomic signature encompasses a large repertoire of genes involved in immunosurveillance.30 These include pattern recognition receptors such as toll-like receptors (TLRs), scavenger receptors and triggering receptor expressed on myeloid cells 2 (TREM2). Moreover, mature microglia express the receptors P2RY12 and P2RY13, conferring exquisite sensitivity to purinergic stimuli. Secondly, their long, elaborately branched processes are remarkably motile, undergoing extremely dynamic, rapid rearrangements and making contact with surrounding CNS cells on a constant basis.31,32 Thus, via their extensive sensome and unceasing motility, microglia scan the entire CNS space once every few hours, and are the primary responders to any disturbance in CNS homeostasis.
Nucleotide pyrophosphatase/phosphodiesterases (NPPs) including NPP1 and NPP2/ ATX as important drug targets: A patent review (2015-2020)
Published in Expert Opinion on Therapeutic Patents, 2022
Sehrish Bano, Mariya Al-Rashida, Rima D Alharthy, Imtiaz Ali Khan, Jamshed Iqbal
Extracellular nucleosides and nucleotides are crucial signaling molecules that control a variety of biological functions by binding to their respective receptors that are located on the cell surface and are termed as purinergic receptors [1]. Ectonucleotidases are a large group of extracellular enzymes that includes members such as ecto-nucleoside pyrophosphatases/phosphodiesterases (NPPs), ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), ecto-5’-nucleotidase (e5ʹNT, CD73) and alkaline phosphatases (APs). They catalyze the hydrolysis of (mono-, di-, and tri-) nucleotides and dinucleoside polyphosphates, thereby yielding extracellular cell-signaling molecules, that is nucleosides (including di- and mono nucleosides), and phosphate and inorganic pyrophosphate (PPi) [2–4]. Hence, ectonucleotidases are responsible for mediating the availability of these cell-signaling molecules at their specific receptors, namely P1 and P2 receptors. The P1 receptors are only activated by binding of adenosine and are further divided into A1, A2A, A2B, and A3 subtypes. On the other hand, the P2 receptors are activated by nucleotides and are further subdivided into P2X (ionotropic, having seven subtypes P2X1–P2X7) and P2Y (G protein-coupled, having P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14) subtypes. The main substrate for NTPDase is nucleoside di- and triphosphates, and nucleoside monophosphate is the major product as a result of its catalytic activity, whereas e5NT exclusively hydrolyzes adenosine monophosphate (AMP) to adenosine. APs and NPPs are rather promiscuous in the sense that although the preferred substrates for hydrolysis are still nucleosides, they hydrolyze a variety of non-nucleotidase substrates as well.