title: Functional interactions between nicotinic and P2X receptors in celiac ganglia neurons.
abstract: Here we characterized the cross-inhibitory interactions between nicotinic and P2X receptors of celiac neurons from the guinea pig by recording whole-cell currents induced by 1mM ACh (I(ACh)), 1mM ATP (I(ATP)) and by the simultaneous application of both agonists (I(ACh)(+ATP)). I(ACh) and I(ATP) were inhibited by hexamethonium (nicotinic channel blocker) and PPADS (P2X receptor antagonist), respectively. The amplitude of I(ACh)(+ATP) was equal to the current induced by the most effective agonist, indicating a current occlusion. Various observations indicate that I(ACh)(+ATP) is carried out through both nicotinic (nACh) and P2X channels: i) I(ACh)(+ATP) desensitisation kinetics were in between that of I(ACh) and I(ATP); ii) application of ATP+ACh, decreased I(ACh) and I(ATP), whereas no cross-desensitisation was observed between nACh and P2X receptors; iii) ATP did not affect I(ACh) in the presence of PPADS or after P2X receptor desensitisation; and iv) ACh did not affect I(ATP) when nACh channels were blocked with hexamethonium or after nACh receptor desensitisation. Current occlusion is not mediated by activation of metabotropic receptors as it is: i) voltage dependent (was not observed at + 5 mV); ii) present at low temperature (10 degrees C) and after inhibition of protein kinase activity (with staurosporine); and iii) absent at 30 microM ATP and 30 microM ACh (concentrations that should activate metabotropic receptors). In conclusion, current occlusion described here is similar to the previously reported myenteric neurons. This occlusion is likely the result of allosteric interactions between these receptors.
authors.affiliation: División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, SLP, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ochoa-Cortés
authors.forename: Luz María
authors.initials: LM
authors.lastname: García-Hernández
authors.forename: Rosa
authors.initials: R
authors.lastname: Espinosa-Luna
authors.forename: Marcela
authors.initials: M
authors.lastname: Miranda-Morales
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montaño
authors.forename: Carlos
authors.initials: C
authors.lastname: Barajas-López
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005728:Ganglia, Sympathetic / Q000166:cytology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X
chemical_list: D018678:Cholinergic Agents; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium