Pürinerjik Sinyal Sistemi ve Diyabet

Yıl 2024, Cilt: 7 Sayı: 3, 125 - 134, 15.11.2024

Süleyman İnce , Ahu Soyocak

Öz

"Pürinerjik" terimi, 1972'de Geoffrey Burnstock tarafından tanımlanmış ve nükleotidlerin hücre dışı sinyal molekülleri olarak işlev gördüğü ortaya konulmuştur. İlerleyen araştırmalar, ATP'nin bir nörotransmiter olarak rol oynadığını ve adenozin, ADP, UTP, UDP gibi diğer nükleotidlerin de hücresel süreçlerde önemli olduğunu göstermiştir. Burnstock'un çalışmaları, pürinerjik reseptörlerin kanser, enflamatuar hastalıklar, kardiyovasküler hastalıklar ve diyabet gibi birçok hastalığın mekanizmalarında etkili olduğunu göstermektedir. Pürinerjik reseptörler, P1 ve P2 olmak üzere iki ana gruba ayrılır. P1 reseptörleri, adenozin tarafından aktive edilir ve A1, A2A, A2B, A3 alt tiplerinden oluşur. P2 reseptörleri ise P2X ligand kapılı iyon kanalı ve P2Y G-protein ilişkili reseptörler olarak iki alt sınıfa ayrılır. P2X reseptörleri ATP tarafından, P2Y reseptörleri ise ATP, ADP, UTP ve UDP gibi nükleotidler tarafından aktive edilir. Pürinerjik sistem, diyabet hastalığının patogenezinde ve komplikasyonlarında önemli rol oynar. ATP, pankreatik β hücrelerinde insülin sekresyonunu düzenlerken, adenosin reseptörleri de insülin sekresyonunu ve β hücre proliferasyonunu etkiler. Diyabetin başlangıcında, ATP hasarla ilişkili moleküler modeller (DAMPs) olarak işlev görerek inflamasyona yol açar. Ayrıca, pürinerjik reseptörler metabolik olarak aktif dokularda yaygın olarak ifade edilir ve diyabetin patofizyolojik süreçlerinde kritik rol oynar. Sonuç olarak, pürinerjik sistemin diyabet ve ilgili komplikasyonların tedavisinde potansiyel bir hedef olduğu görülmektedir. Pürinerjik reseptörlerin farmakolojik manipülasyonu, diyabetin yönetiminde yeni tedavi stratejileri geliştirilmesine katkıda bulunabilir.

Anahtar Kelimeler

Pürinerjik Sistem, Diyabet, Pürinerjik Reseptörler

Kaynakça

• Burnstock G. Purinergic nerves. Pharmacol Rev. 1972;24:509–81.
• Burnstock G. Do some nerve cells release more than one transmitter? Comment Neurosci. 1980;151–60.
• Burnstock G. Purine and purinergic receptors. Brain Neurosci Adv. 2018;2:2398212818817494.
• Reichert KP, Castro MFV, Assmann CE, Bottari NB, Miron VV, Cardoso A, et al. Diabetes and hypertension: pivotal involvement of purinergic signaling. Biomed Pharmacother. 2021;137:111273.
• Burnstock G. Purinergic receptors. J Theor Biol. 1976;62(2):491–503.
• Burnstock G. A basis for distinguishing two types of purinergic receptor. Cell Membr Recept Drugs Horm A Multidiscip Approach. 1978;107–18.
• Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, et al. Selective amplification and cloning of four new members of the G protein- coupled receptor family. Science (80- ). 1989;244(4904):569–72.
• Zhou Q-Y, Li C, Olah ME, Johnson RA, Stiles GL, Civelli O. Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor. Proc Natl Acad Sci. 1992;89(16):7432–6.
• Reshkin SJ, Guerra L, Bagorda A, Debellis L, Cardone R, Li AH, et al. Activation of A3 adenosine receptor induces calcium entry and chloride secretion in A6 cells. J Membr Biol. 2000;178(2):103–13.
• Jacobson KA, Balasubramanian R, Deflorian F, Gao Z-G. G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal. 2012;8(3):419–36.
• Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50(3):413–92.
• Abbracchio MP, Burnstock G. Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther. 1994;64(3):445–75.
• Burnstock G, Kennedy C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol Vasc Syst. 1985;16(5):433–40.
• Kaczmarek-Hájek K, Lörinczi É, Hausmann R, Nicke A. Molecular and functional properties of P2X receptors—recent progress and persisting challenges. Purinergic Signal. 2012;8(3):375–417.
• Hattori M, Gouaux E. Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature. 2012;485(7397):207–12.
• North RA. Molecular physiology of P2X receptors. Physiol Rev. 2002;82(4):1013– 67.
• von Kügelgen I, Harden TK. Molecular pharmacology, physiology, and structure of the P2Y receptors. Adv Pharmacol. 2011;61:373–415.
• Abbracchio MP, Boeynaems J-M, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, et al. Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci. 2003;24(2):52–5.
• Abbracchio MP. Update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev. 2006;58:281–341.
• Parravicini C, Ranghino G, Abbracchio MP, Fantucci P. GPR17: molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors. BMC Bioinformatics. 2008;9(1):1–19.
• Burnstock G. Discovery of purinergic signalling, the initial resistance and current explosion of interest. Br J Pharmacol. 2012;167(2):238–55.
• Le Duc D, Schulz A, Lede V, Schulze A, Thor D, Brüser A, et al. P2Y receptors in Immunol. 2017;136:85–121.
• Lovászi M, Haas CB, Antonioli L, Pacher P, Haskó G. The role of P2Y receptors in regulating immunity and metabolism. Biochem Pharmacol. 2021;187:114419.
• Lustig KD, Shiau AK, Brake AJ, Julius D. Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc Natl Acad Sci. 1993;90(11):5113–7.
• Nicholas RA, Watt WC, Lazarowski ER, Li Q, Harden K. Uridine nucleotide selectivity of three phospholipase C-activating - lective, a UTP-selective, and an ATP-and 1996;50(2):224–9.
• Chambers JK, Macdonald LE, Sarau HM, Ames RS, Freeman K, Foley JJ, et al. AG protein-coupled receptor for UDP-glucose. J Biol Chem. 2000;275(15):10767–71.
• Bodor ET, Waldo GL, Hooks SB, Corand functional reconstitution of the human P2Y12 receptor. Mol Pharmacol. 2003;64(5):1210–6.
• Marteau F, Le Poul E, Communi D, Communi D, Labouret C, Savi P, et al. Pharmacological characterization of the human P2Y13 receptor. Mol Pharmacol. 2003;64(1):104–12.
• Bartlett R, Stokes L, Sluyter R. The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease. Pharmacol Rev. 2014;66(3):638– 75.
• Burnstock G. Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev. 2006;58(1):58–86.
• Ai Y, Wang H, Liu L, Qi Y, Tang S, Tang J, et al. Purine and purinergic receptors in health and disease. MedComm. 2023;4(5):e359.
• de Lima AC, Chaves LM, Prestes SN, Mânica A, Cardoso AM. The purinergic sig- - nesis and progression of diabetes: key fa- 2022;71(7–8):759–70.
• Burnstock G, Novak I. Purinergic signalling and diabetes. Purinergic Signal. 2013;9(3):307–24.
• Burnstock G. Purinergic signalling: Its unpopular beginning, its acceptance and its exciting future. Bioessays. 2012;34(3):218–25.
• Garcia-Jacobo RE, Bergamin LS, Vultaggio- Poma V, Thorstenberg ML, Tarantini M, García-Hernández MH, et al. The purinergic landscape of type 2 diabetes mellitus. Molecules. 2022;27(6):1838.
• Sapra A, Bhandari P. Diabetes. In: Stat- Pearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 31855345.; 2023.
• https://idf.org/about-diabetes/diabetes-fa-
• Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.
• Jain S, Jacobson KA. Purinergic signaling in diabetes and metabolism. Biochem Pharmacol. 2021;187:114393.
• Novak I. Purinergic receptors in the endocrine and exocrine pancreas. Purinergic Signal. 2008;4:237–53.
• Antonioli L, Blandizzi C, Csóka B, Pacher P, Haskó G. Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations. Nat Rev Endocrinol. 2015;11(4):228–41.
• Mikhail TH, Awadallah R. The effect of ATP and certain trace elements on the induction of experimental diabetes. Z Ernahrungswiss. 1977;16:176–83.
• Zhou R, Dang X, Sprague RS, Mustafa SJ, Zhou Z. Alteration of purinergic signaling in diabetes: focus on vascular function. J Mol Cell Cardiol. 2020;140:1–9.
• Vindeirinho J, Costa GN, Correia MB, Cavadas C, Santos PF. Effect of diabetes/hyperglycemia on the rat retinal adenosinergic system. PLoS One. 2013;8(6):e67499.
• Sugiyama T, Kobayashi M, Kawamura H, Li Q, Puro DG. Enhancement of P2X7-induced pore formation and apoptosis: an early effect of diabetes on the retinal microvasculature. Invest Ophthalmol Vis Sci. 2004;45(3):1026–32.
• Sugiyama T, Kawamura H, Yamanishi S, Kobayashi M, Katsumura K, Puro DG. Regulation of P2X7-induced pore formation and cell death in pericyte-containing retinal microvessels. Am J Physiol Physiol. 2005;288(3):C568–76.
• Migita K, Moriyama T, Koguchi M, Honda K, Katsuragi T, Takano Y, et al. Modulation of P2X receptors in dorsal root ganglion neurons of streptozotocin-induced diabetic neuropathy. Neurosci Lett. 2009;452(2):200–3.