Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons.
Inhibitory interactions between 5-HT subtype 3 (5-HT(3)) and P2X receptors were characterized using whole cell recording techniques. Currents induced by 5-HT (I(5-HT)) and ATP (I(ATP)) were blocked by tropisetron (or ondansetron) and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, respectively. Currents induced by 5-HT + ATP (I(5-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 I(5-HT+ATP) indicate that they are carried through 5-HT(3) and P2X channels. Current occlusion occurred as fast as activation of I(5-HT) and I(ATP), was still present in the absence of Ca(2+) or Mg(2+), 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 degrees C, 23 degrees C, and 8 degrees C. These results are in agreement with a model that considers that 5-HT(3) and P2X channels are in functional clusters and that these channels might directly inhibit each other.
Barajas-López
Carlos
C
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada. barajasc@meds.queensu.ca
Montaño
Luis M
LM
Espinosa-Luna
Rosa
R
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D004347:Drug Interactions; D004361:Drug Tolerance; D004553:Electric Conductivity; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D007583:Jejunum / Q000502:physiology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology
D010750:Phosphoproteins; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D002586:Cesium; D012701:Serotonin; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D008274:Magnesium; D002118:Calcium