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

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. The amount of specific binding did not differ at a room temperature of 20-25 degrees C or 0-4 degrees C, and equilibration occurred within 10 min. Divalent cations (Ca2+, Mg2+, Mn2+ and Ni2+) and monovalent cations (Na+ and K+) did not increase the specific binding, yet in higher concentrations, they decreased both specific and non-specific binding. Specific binding showed a single component, Kd and Bmax of which were 6.35 microM and 79 pmol/mg protein, respectively. 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. Bmax 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 Kd values did not differ. These results indicate that specific 3H-baclofen binding in the rat peripheral tissues is entirely different from the binding in the central nervous system (GABAB sites).