Species variations in RU 24969 interactions with non-5-HT1A binding sites

The interaction of RU 24969 with [3H]5-hydroxytryptamine ([3H]5-HT) binding to non-5-HT1A binding sites was analyzed in nine species. Non-5-HT1A binding was defined as specific [3H]5-HT binding observed in the presence of 100 nM 8-OH-DPAT. Computer-assisted iterative curve fitting of RU 24969 competition studies indicate that RU 24969 distinguishes two distinct components of non-5-HT1A sites in rat and mouse brain. These two binding components display apparent Ki values of 0.33-0.39 and 66-130 nM for RU 24969. By contrast, RU 24969 competition for non-5-HT1A binding in guinea-pig, cow, human, dog, chicken, turtle and frog brain membranes is consistent with a homogeneous population of [3H]5-HT binding sites. This population of sites displays apparent Ki values of 23-130 nM for RU 24969 and appear to be analogous to the low affinity component of non-5-HT1A sites identified in rat and mouse.