Increased 5-HT(3)-mediated signalling in pelvic afferent neurons from mice deficient in P2X(2) and/or P2X (3) receptor subunits.

Purinergic Signalling
Bei MaG Burnstock

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 alpha,beta-methylene ATP (alpha,beta-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 res...Continue Reading

References

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Apr 3, 2001·Trends in Pharmacological Sciences·G Burnstock
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Nov 5, 2003·Gastroenterology·Gregory WynnGeoffrey Burnstock

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Citations

Feb 15, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Laszlo KölesPeter Illes
May 2, 2012·Purinergic Signalling·Karina Kaczmarek-HájekAnnette Nicke
Sep 25, 2007·The Journal of Biological Chemistry·Zoltan GerevichPeter Illes

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