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Am J Physiol Gastrointest Liver Physiol 283: G1238-G1248, 2002. First published June 5, 2002; doi:10.1152/ajpgi.00054.2002
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Vol. 283, Issue 6, G1238-G1248, December 2002

Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons

Carlos Barajas-López1, Luis M. Montaño2, and Rosa Espinosa-Luna1

1 Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada; and 2 Instituto Nacional de Enfermedades Respiratorias and Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, México D.F, México

Inhibitory interactions between 5-HT subtype 3 (5-HT3) and P2X receptors were characterized using whole cell recording techniques. Currents induced by 5-HT (I5-HT) and ATP (IATP) were blocked by tropisetron (or ondansetron) and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, respectively. Currents induced by 5-HT + ATP (I5-HT+ATP) were only as large as the current induced by the most effective transmitter, revealing current occlusion. Occlusion was observed at membrane potentials of -60 and 0 mV (for inward currents), but it was not present at +40 mV (for outward currents). Kinetic and pharmacological properties of I5-HT+ATP indicate that they are carried through 5-HT3 and P2X channels. Current occlusion occurred as fast as activation of I5-HT 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 proportional to ,beta -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 5-HT3 and P2X channels are in functional clusters and that these channels might directly inhibit each other.

autonomic neurons; enteric neurons; ligand-gated channels; ion channels; ATP; ATP receptors; P2X receptors; serotonin; 5-hydroxytryptamine; 5-hydroxytryptamine 3 channels; 5-hydroxytryptamine 3 receptors; fast neurotransmission


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