Two suramin binding sites are present in guinea pig but only one in murine native P2X myenteric receptors.
Whole-cell patch clamp recordings were used to characterise the physiological and pharmacological properties of P2X receptors of mouse and guinea pig myenteric neurons from the small intestine. ATP application induced a rapid inward current in 95% of recorded neurons of both species when were voltage clamped at -60 mV. Concentration-response curves for ATP (1-3000 microM) yielded EC(50) values of 114 and 115 microM for mouse and guinea pig myenteric neurons, respectively, with a Hill coefficient value of 1.02 and 0.79, respectively, which were not significantly different of unity. alpha,beta-methylene ATP (100 microM) was virtually inactive in both species. Pyridoxalphophate-6-azophenyl-2',4'-disulphonic acid (0.01-30 microM) inhibited the ATP-induced currents (I(ATP)) with a different potency; being the IC(50) 0.6 and 1.8 microM in mouse and guinea pig, respectively. In mouse myenteric neurons, I(ATP) were inhibited by suramin whereas in guinea pig neurons we observed two effects, potentiation and inhibition of these currents. On guinea pig, both effects of suramin had different recovering kinetics and concentration dependency, indicating that they are mediated by at least two different binding sites. Our observations indicate that myenteric P2X receptors in these two species have different pharmacological properties.
Guerrero-Alba
Raquel
R
División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, SLP CP78216, Mexico.
Valdez-Morales
Eduardo
E
Juárez
Esri H
EH
Miranda-Morales
Marcela
M
Ramírez-Martínez
Juan F
JF
Espinosa-Luna
Rosa
R
Barajas-López
Carlos
C
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001696:Biomechanical Phenomena; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009197:Myenteric Plexus; D058910:Purinergic P2 Receptor Agonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D013498:Suramin / Q000378:metabolism* / Q000494:pharmacology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate