NDLI: Increased 5-HT$_{3}$-mediated signalling in pelvic afferent neurons from mice deficient in P2X$_{2}$ and/or P2X$

Content Provider	Springer Nature Link
Author	Ma, Bei Wynn, Gregory Dunn, Philip M. Burnstock, Geoffrey
Copyright Year	2006
Abstract	Extracellular ATP and 5-hydroxytryptamine (5-HT) are both involved in visceral sensory pathways by interacting with P2X and 5-HT$_{3}$ receptors, respectively. We have investigated the changes in P2X and 5-HT$_{3}$-mediated signalling in pelvic afferent neurons in mice deficient in P2X$_{2}$ and/or P2X$_{3}$ subunits by whole-cell recording of L$_{6}$–S$_{2}$ dorsal root ganglion (DRG) neurons and by multi-unit recording of pelvic afferents of the colorectum. In wildtype DRG neurons, ATP evoked transient, sustained or mixed (biphasic) inward currents. Transient currents were absent in P2X$_{3}$ $^{−/−}$ neurons, whereas sustained currents were absent in P2X$_{2}$ $^{−/−}$ DRG neurons. Neither transient nor sustained currents were observed following application of ATP or α,β-methylene ATP (α,β-meATP) in P2X$_{2}$/P2X$_{3}$ $^{Dbl−/−}$ DRG neurons. 5-HT was found to induce a fast inward current in 63% of DRG neurons from wildtype mice, which was blocked by tropisetron, a 5-HT$_{3}$ receptor antagonist. The percentage of DRG neurons responding to 5-HT was significantly increased in P2X $_{2}$ $^{−/−}$, P2X$_{3}$ $^{−/−}$ and P2X$_{2}$/P2X$_{3}$ $^{Dbl−/−}$ mice, and the amplitude of 5-HT response was significantly increased in P2X$_{2}$/P2X$_{3}$ $^{Dbl−/−}$ mice. The pelvic afferent response to colorectal distension was attenuated in P2X$_{2}$/P2X$_{3}$ $^{Dbl−/−}$ mice, but the response to serosal application of 5-HT was enhanced. Furthermore, tropisetron resulted in a greater reduction in pelvic afferent responses to colorectal distension in the P2X$_{2}$/P2X$_{3}$ $^{Dbl−/−}$ preparations. These data suggest that P2X receptors containing the P2X$_{2}$ and/or P2X$_{3}$ subunits mediate purinergic activation of colorectal afferents and that 5-HT signalling in pelvic afferent neurons is up-regulated in mice lacking P2X$_{2}$ or P2X$_{3}$ receptor genes. This effect is more pronounced when both subunits are absent.
Starting Page	481
Ending Page	489
Page Count	9
File Format	PDF
ISSN	15739538
Journal	Purinergic Signalling
Volume Number	2
Issue Number	3
e-ISSN	15739546
Language	English
Publisher	Springer Netherlands
Publisher Date	2006-07-04
Publisher Institution	International Purine Club
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	pelvic afferents P2X receptors 5-HT Biomedicine general Pharmacology/Toxicology Human Physiology Neurosciences Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Cellular and Molecular Neuroscience

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