TY - JOUR T1 - Pharmacology of δ2 Glutamate Receptors: Effects of Pentamidine and Protons JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 740 LP - 748 DO - 10.1124/jpet.102.045799 VL - 305 IS - 2 AU - Keith Williams AU - Michael Dattilo AU - Thomas N. Sabado AU - Keiko Kashiwagi AU - Kazuei Igarashi. Y1 - 2003/05/01 UR - http://jpet.aspetjournals.org/content/305/2/740.abstract N2 - The properties of δ2 receptors, which have homology to glutamate receptors but are not gated by glutamate, were studied using the constitutively active Lurcher mutant δ2(A654T) expressed in Xenopus oocytes. The macroscopic current through δ2(A654T) channels in voltage-clamped oocytes was defined as the difference between the holding current measured in the presence of extracellular Na+ and that in the presence of the large impermeant cation N-methyl-d-glucamine. A-to-T mutations in the δ1 subunit and in NMDA (N-methyl-d-aspartate) receptor subunits, at positions equivalent to δ2(A654T), did not produce constitutively active channels. The current through δ2(A654T) channels was reduced by pentamidine and 9-tetrahydroaminoacridine, antagonists that also inhibit NR1/NR2B NMDA receptors but not AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. Block of δ2(A654T) currents by these two antagonists was incomplete and weakly voltage-dependent, in contrast to the block of NR1/NR2B receptors, which was complete and strongly voltage-dependent. Pentamidine inhibited a constitutively active NR1(T648A)/NR2B NMDA receptor in a manner similar to its inhibition of a glutamate-gated wild-type NMDA receptor, but different from its inhibition of constitutively active δ2(A654T) receptors. Currents gated by δ2(A654T) were sensitive to the extracellular pH, being smaller at acidic than at alkaline pH, with a pH IC50 value of 7.47 and a maximum inhibition of 70%. It is concluded that δ2(A654T) channels have some properties in common with NMDA channels but also have characteristics that are different from these receptors. Compounds such as pentamidine may be useful for studies of native δ2 receptors. The American Society for Pharmacology and Experimental Therapeutics ER -