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Am J Physiol Gastrointest Liver Physiol (June 5, 2002). doi:10.1152/ajpgi.00054.2002
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Articles in PresS, published online ahead of print June 5, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00054.2002
Submitted on February 11, 2002
Accepted on May 8, 2002

Inhibitory Interactions Between 5HT3 and P2X Channels in Submucosal Neurons

Carlos Barajas-Lopez1*, Luis M Montano2, and Rosa Espinosa-Luna1

1 Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada
2 Fac. de Medicina, INER and Depto. de Farmacolog a, Mexico, D.F., Mexico; Fac. de Medicina, INER and Depto. de Farmacolog a, Mexico, D.F., Mexico

* To whom correspondence should be addressed. E-mail: barajasc{at}meds.queensu.ca.

Inhibitory interactions between 5HT3 and P2X receptors were characterized using whole-cell recording techniques. Currents induced by serotonin (I5HT) and ATP (IATP) were blocked by tropisetron (or ondansetron) and PPADS, respectively. Currents induced by serotonin+ATP (I5HT+ATP) were only as large as the current induced by the most effective transmitter, revealing current occlusion. Occlusion was observed at a membrane potential of -60 and 0 mV (for inward currents), but it was not present at +40 mV (for outward currents). Kinetic and pharmacological properties of I5HT+ATP indicate that they are carried through 5HT3 and P2X channels. Current occlusion occurred as fast as activation of I5HT and IATP, was still present in the absence of Ca2+ or Mg2+, after adding staurosporine, genistein, K-252a, or N-ethylmaleimide to the pipette solution, after substituting ATP with {alpha},ß-methylene ATP, or GTP with GTP-{gamma}-S in the pipette, and was observed at 35°C, 23°C, and 8°C. These results are in agreement with a model that considers that 5HT3 and P2X channels are in functional clusters and that these channels might directly inhibit each other.




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