Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis

Borvendeg, Sebestyén J.; Al-Khrasani, Mahmoud; Rubini, Patrizia; Fischer, Wolfgang B.; Allgaier, Clemens; Wirkner, Kerstin; Himmel, Herbert M.; Gillen, Clemens; Illéš, Peter

doi:10.1016/s0014-2999(03)02003-x

Cited by 10 publications

(2 citation statements)

References 11 publications

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“…The up-regulation of P2X 2 and P2X 3 receptors in interstitial cystitis was accompanied by an elevated protein expression, and a decrease in P2X 3 gene expression, whereas the expression of the P2X 2 gene remained unchanged [160,161]. In contrast to the up-regulation of P2X 3 receptors in urothelium in interstitial cystitis, P2X 3 (and/or P2X 2/3 ) receptor activity in lumbrosacral dorsal root ganglion neurons innervating the urinary bladder was decreased in the rat model of cyclophosphamide-induced cystitis [162].…”

Section: P2x 3 Receptors In Visceral Painmentioning

confidence: 85%

P2X3 Receptor Involvement in Pain States

2007

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The understanding of how pain is processed at each stage in the peripheral and central nervous system is the precondition to develop new therapies for the selective treatment of pain. In the periphery, ATP can be released from various cells as a consequence of tissue injury or visceral distension and may stimulate the local nociceptors. The highly selective distribution of P2X(3) and P2X(2/3) receptors within the nociceptive system has inspired a variety of approaches to elucidate the potential role of ATP as a pain mediator. Depolarization by ATP of neurons in pain-relevant neuronal structures such as trigeminal ganglion, dorsal root ganglion, and spinal cord dorsal horn neurons are well investigated. P2X receptor-mediated afferent activation appears to have been implicated in visceral and neuropathic pain and even in migraine and cancer pain. This article reviews recently published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance of the P2X(3) receptor in different states of pain.

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Section: P2x 3 Receptors In Visceral Painmentioning

confidence: 85%

P2X3 Receptor Involvement in Pain States

2007

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“…Behavioral studies indicated a strong pain reaction developing within 2 h and leveling off thereafter causing a constant pain during the following 18 h. , -meATP induced less increase in [Ca2+]i in the cyclophosphamide-treated animals than in saline-treated counterparts. Hence, , -meATP-sensitive P2X3 and/or P2X2/3 receptors of the L6/S1 dorsal root ganglion neurons were functionally down-regulated during subacute pain in experimental cystitis [31]. Understanding the normal expression of P2X2 and P2X3 receptors in bladder urothelium may be important for the development of effective therapies for IC, by providing new drug targets [29].…”

Section: P2 Receptors In Urinary Bladdermentioning

confidence: 99%

Purinergic (P2) Receptor Control of Lower Genitourinary Tract Function and New Avenues for Drug Action: An Overview

Gür

Kadowitz²

2007

CPD

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Micturition, penile erection, contraction of prostatic smooth muscle, peristalsis of the male excurrent duct system and lumbosacral spinal cord neurotransmission all require adenosine 5'-triphosphate (ATP) activity and this likely involves purinergic (P2) receptors. P2 receptors are categorized as either ligand-gated ionotropic P2X or metabotropic G-protein-coupled P2Y subtypes. In the urinary bladder, purinergic receptor mechanisms are involved in both motor and sensory function. In the prostate, P2X1-receptors, which mediate contraction, are present in the fibromuscular stroma while G protein-coupled P2Y purinoceptors have a wide range of actions in prostate cancer. In the excretory ducts of the testis (ductus epididymidis, vas deferens and its associated seminal vesicles), heavy immunostaining for P2X1 and P2X2 subtypes is detected in the membranes of smooth muscle, suggesting their role in sperm transport and ejaculation. In the penis, intense P2X1 and weak P2X2 immunoreactivity are observed in smooth muscle of blood vessels and the corpus cavernosum, implying their participation in detumescence. Human corporal cavernosum stimulation induces relaxation of P2Y purinoceptors. Targeting of extracellular or intracellular P2X and/or P2Y receptor signaling pathways holds promise in affecting the lower genitourinary tract system. Our advancing knowledge about purine agonists and their pharmacologic benefits in erectile, ejaculatory, urinary bladder and prostatic hyperplasia may service clinical problems in the near future.

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Purines and Sensory Nerves

Burnstock¹

2009

Handbook of Experimental Pharmacology

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P2X and P2Y nucleotide receptors are described on sensory neurons and their peripheral and central terminals in dorsal root, nodose, trigeminal, petrosal, retinal and enteric ganglia. Peripheral terminals are activated by ATP released from local cells by mechanical deformation, hypoxia or various local agents in the carotid body, lung, gut, bladder, inner ear, eye, nasal organ, taste buds, skin, muscle and joints mediating reflex responses and nociception. Purinergic receptors on fibres in the dorsal spinal cord and brain stem are involved in reflex control of visceral and cardiovascular activity, as well as relaying nociceptive impulses to pain centres. Purinergic mechanisms are enhanced in inflammatory conditions and may be involved in migraine, pain, diseases of the special senses, bladder and gut, and the possibility that they are also implicated in arthritis, respiratory disorders and some central nervous system disorders is discussed. Finally, the development and evolution of purinergic sensory mechanisms are considered.

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Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis

Cited by 10 publications

References 11 publications

P2X3 Receptor Involvement in Pain States

P2X3 Receptor Involvement in Pain States

Purinergic (P2) Receptor Control of Lower Genitourinary Tract Function and New Avenues for Drug Action: An Overview

Purines and Sensory Nerves

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