title: Effects of ATP antagonists on purinoceptor-operated inward currents in rat phaeochromocytoma cells.
abstract: The effects of suramin, reactive blue 2 (RB2) and d-tubocurarine (d-TC) were investigated electrophysiologically to elucidate the mechanisms underlying their antagonism of P2 purinoceptor-mediated responses. All three compounds inhibited an adenosine triphosphate (ATP)-activated inward current in rat phaeochromocytoma PC12 cells in a concentration-dependent manner. The order of potency was RB2 greater than suramin greater than d-TC. The inhibition induced by suramin or RB2 was reversible, whereas that induced by d-TC was not reversed after a 5-min rinse. The inactivation of the ATP-activated current was accelerated by d-TC but not by suramin or RB2. RB2 administered simultaneously with ATP exerted much weaker inhibition compared to that induced by prior administration, suggesting that RB2 is a slowly acting antagonist. This was not observed for suramin or d-TC. Suramin and RB2 caused a parallel shift in the concentration/response curve for the ATP-activated current. With d-TC the maximal response of ATP was decreased but the concentration producing half-maximal response was unchanged. The voltage dependency of the ATP-activated current showed less inward rectification in the presence of d-TC. Suramin or RB2 did not affect the voltage dependency. These results suggest that suramin and RB2 reversibly block binding of ATP to receptors, whereas d-TC blocks ion permeability through the ATP-activated channel.
authors.affiliation: Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakazawa
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Fujimori
authors.forename: A
authors.initials: A
authors.lastname: Takanaka
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000310:Adrenal Gland Neoplasms / Q000503:physiopathology*; D000818:Animals; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D010673:Pheochromocytoma / Q000503:physiopathology*; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D007473:Ion Channels; D011983:Receptors, Purinergic; D014227:Triazines; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate; D014403:Tubocurarine