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P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP.
J Physiol 2005; 567(Pt 2):621-39JP

Abstract

Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors variably composed of P2X2 and P2X3 subunits. P2X2 and P2X3 subunits can form homomultimeric P2X2, homomultimeric P2X3, or heteromultimeric P2X2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood. Here we describe null mutant mice lacking the P2X2 receptor subunit (P2X2-/-) and double mutant mice lacking both P2X2 and P2X3 subunits (P2X2/P2X3(Dbl-/-)), and compare these with previously characterized P2X3-/- mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG) neurones from wild-type mice responded to ATP with sustained inward currents, while dorsal root ganglia (DRG) neurones gave predominantly transient currents. Sensory neurones from P2X2-/- mice responded to ATP with only transient inward currents, while sympathetic neurones had barely detectable responses. Neurones from P2X2/P2X3(Dbl-/-) mice had minimal to no response to ATP. These data indicate that P2X receptors on sensory and sympathetic ganglion neurones involve almost exclusively P2X2 and P2X3 subunits. P2X2-/- and P2X2/P2X3(Dbl-/-) mice had reduced pain-related behaviours in response to intraplantar injection of formalin. Significantly, P2X3-/-, P2X2-/-, and P2X2/P2X3(Dbl-/-) mice had reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. No deficits in a wide variety of CNS behavioural tests were observed in P2X2-/- mice. Taken together, these data extend our findings for P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder.

Authors+Show Affiliations

Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. debra.cockayne@roche.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15961431

Citation

Cockayne, Debra A., et al. "P2X2 Knockout Mice and P2X2/P2X3 Double Knockout Mice Reveal a Role for the P2X2 Receptor Subunit in Mediating Multiple Sensory Effects of ATP." The Journal of Physiology, vol. 567, no. Pt 2, 2005, pp. 621-39.
Cockayne DA, Dunn PM, Zhong Y, et al. P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol (Lond). 2005;567(Pt 2):621-39.
Cockayne, D. A., Dunn, P. M., Zhong, Y., Rong, W., Hamilton, S. G., Knight, G. E., ... Ford, A. P. (2005). P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. The Journal of Physiology, 567(Pt 2), pp. 621-39.
Cockayne DA, et al. P2X2 Knockout Mice and P2X2/P2X3 Double Knockout Mice Reveal a Role for the P2X2 Receptor Subunit in Mediating Multiple Sensory Effects of ATP. J Physiol (Lond). 2005 Sep 1;567(Pt 2):621-39. PubMed PMID: 15961431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. AU - Cockayne,Debra A, AU - Dunn,Philip M, AU - Zhong,Yu, AU - Rong,Weifang, AU - Hamilton,Sara G, AU - Knight,Gillian E, AU - Ruan,Huai-Zhen, AU - Ma,Bei, AU - Yip,Ping, AU - Nunn,Philip, AU - McMahon,Stephen B, AU - Burnstock,Geoffrey, AU - Ford,Anthony P D W, Y1 - 2005/06/16/ PY - 2005/6/18/pubmed PY - 2005/10/28/medline PY - 2005/6/18/entrez SP - 621 EP - 39 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 567 IS - Pt 2 N2 - Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors variably composed of P2X2 and P2X3 subunits. P2X2 and P2X3 subunits can form homomultimeric P2X2, homomultimeric P2X3, or heteromultimeric P2X2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood. Here we describe null mutant mice lacking the P2X2 receptor subunit (P2X2-/-) and double mutant mice lacking both P2X2 and P2X3 subunits (P2X2/P2X3(Dbl-/-)), and compare these with previously characterized P2X3-/- mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG) neurones from wild-type mice responded to ATP with sustained inward currents, while dorsal root ganglia (DRG) neurones gave predominantly transient currents. Sensory neurones from P2X2-/- mice responded to ATP with only transient inward currents, while sympathetic neurones had barely detectable responses. Neurones from P2X2/P2X3(Dbl-/-) mice had minimal to no response to ATP. These data indicate that P2X receptors on sensory and sympathetic ganglion neurones involve almost exclusively P2X2 and P2X3 subunits. P2X2-/- and P2X2/P2X3(Dbl-/-) mice had reduced pain-related behaviours in response to intraplantar injection of formalin. Significantly, P2X3-/-, P2X2-/-, and P2X2/P2X3(Dbl-/-) mice had reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. No deficits in a wide variety of CNS behavioural tests were observed in P2X2-/- mice. Taken together, these data extend our findings for P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/15961431/P2X2_knockout_mice_and_P2X2/P2X3_double_knockout_mice_reveal_a_role_for_the_P2X2_receptor_subunit_in_mediating_multiple_sensory_effects_of_ATP_ L2 - https://doi.org/10.1113/jphysiol.2005.088435 DB - PRIME DP - Unbound Medicine ER -