Abstract
The concept of a purinergic signaling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief introduction and update of purinoceptor subtypes, this article focuses on the diverse pathophysiological roles of purines and pyrimidines as signaling molecules. These molecules mediate short-term (acute) signaling functions in neurotransmission, mechanosensory transduction, secretion and vasodilatation, and long-term (chronic) signaling functions in cell proliferation, differentiation, and death involved in development and regeneration. Plasticity of purinoceptor expression in pathological conditions is frequently observed, including an increase in the purinergic component of autonomic cotransmission. Recent advances in therapies using purinergic-related drugs in a wide range of pathological conditions will be addressed with speculation on future developments in the field.
Footnotes
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↵1 Abbreviations: NANC, nonadrenergic, noncholinergic; NO, nitric oxide; E-NTPDase, ectonucleoside triphosphate diphosphohydrolase; NA, noradrenaline; DRG, dorsal root ganglia; PPADS; pyridoxal-5′-phosphate-6-azophenyl-2′,4′ disulfonic acid; TNP, trinitrophenyl; NMDA, N-methyl-d-aspartate; AIT-082, 4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; LTP, long-term potentiation; NTS, nucleus tractus solitarius; Ap4A, diadenosine tetraphosphate; IL, interleukin; COX, cyclooxygenase; CNS, central nervous system; IB4, isolectin B4; IBD, inflammatory bowel disease; MRS2500, 2-iodo-N6-methyl-(N)-methanocarba-20-deoxyadenosine-30,50-bisphosphate; A-317491, 5-([(3-phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid; INS37217, P1-(uridine 5′)-P4-(2′-deoxycytidine 5′)tetraphosphate, tetrasodium salt.
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Article, publication date, and citation information can be found at http://pharmrev.aspetjournals.org.
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doi:10.1124/pr.58.1.5.
- The American Society for Pharmacology and Experimental Therapeutics
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