1. A high density of [3H]-PK 11195 binding sites was present in gerbil cortical membranes (B(max) [3H]-PK 11195 1360 ± 71 fmol mg-1 protein) in comparison to rat cortical membranes (254 ± 21 fmol mg-1 protein). This effect was species-specific as similar findings were obtained with hippocampal membranes (B(max) 1430 ± 111 fmol mg-1 protien in gerbil, compared to 196 ± 31 in rat). 2. RO 5-4864, also a peripheral type benzodiazepine compound, displayed low affinity for the [3H]-PK 11195 site in the gerbil (pK(i) 6.57 ± 0.02 and 6.70 ± 0.12 in hippocampus and cortex respectively) compared to rat (pK(i) 8.16 ± 0.07 and 8.48 ± 0.02). Central benzodiazepine compounds, diazepam and flunitrazepam, also diaplayed this trend. 3. RO 5-4864 displaced [3H]-PK 11195 binding from gerbil and rat cortical membranes through a competitive interaction with Hill slopes close to unity. In both tissues, saturation isotherms of [3H]-PK 11195 binding indicated that the presence of RO 5-4864 caused chages in K(d) without any effect on B(max). In kinetic experiments, the presence of RO 5-4864 failed to modify the rate of dissociation of [3H]-PK 11195 from equilibrium in both rat and gerbil cortical membranes. 4. Forebrain ischaemia in the Mongolian gerbil (5 min bilateral carotid artery occlusion) with 7 days recovery caused a significant (P < 0.05) decrease in the density of hippocampal 5-HT(1A) binding sites labelled by [3H]-8-OH-DPAT (B(max) control, 393 ± 33 fmol mg-1 protein; ischaemic, 289 ± 21 fmol mg-1 protein) and an increase (P < 0.01) in [3H]-PK 11195 binding sites (B(max) control, 1430 ± 111 fmol mg-1 protein; ischaemic, 2160 ± 170 fmol mg-1 protein). Ischaemia and recovery had no effect on the affinity of either ligand.
|Number of pages||6|
|Journal||British Journal of Pharmacology|
|Publication status||Published - 1993|
- [3H]-PK 11195
- Forebrain ischaemia