The non-GABAergic nature of 3H-baclofen binding in rat peripheral tissues

Abstract

1. 1. In peripheral tissues from organs such as the kidney, liver and spleen, specific binding of 3H-baclofen was most highly detected in the kidney, and that in the liver and spleen was approximately one-tenth that in the kidney. 2. 2. The amount of specific binding did not differ at a room temperature of 20–25°C or 0–4°C, and equilibration occurred within 10 min. 3. 3. Divalent cations (Ca 2+, Mg 2+, Mn 2+ and Ni 2+) and monovalent cations (Na + and K +) did not increase the specific binding, yet in higher concentrations, they decreased both specific and non-specific binding. 4. 4. Specific binding showed a single component, K d and B max of which were 6.35 μM and 79 pmol/mg protein, respectively. 5. 5. The binding was stereospecific; (−)baclofen was 150 times as potent as (+)baclofen. Some of the structural analogues of baclofen inhibited 3H-baclofen binding whereas GABA and its related compounds showed little or no inhibition. 6. 6. B max of the binding in the kidney of spontaneously hypertensive rats (SHR) was higher by 28% than that of normotensive Wistar-Kyoto rats (WKY), whereas the K d values did not differ. 7. 7. These results indicate that specific 3H-baclofen binding in the rat peripheral tissues is entirely different from the binding in the central nervous system (GABA B sites).