NONADRENERGIC BINDING-SITES FOR THE ALPHA-2-ANTAGONIST [H-3] IDAZOXAN IN RABBIT URETHRAL SMOOTH-MUSCLE

In the present study, we have provided evidence that [H-3] idazoxan bind to different sites in rabbit urethra. The [H-3] idazoxan capacity and affinity was 215 +/- 14 fmol/mg protein and 1.59 +/- 0.16 nM while [H-3] rauwolscine binding parameters were 45.9 +/- 3.4 fmol/mg protein and 2.39 +/- 0.27 nM. [H-3] idazoxan specific binding was inhibited only by compounds possessing an imidazoli(di)ne or a guanidinium moiety, while [H-3] rauwolscine specific binding was inhibited by phenylethanolamines and classical alpha-2-antagonists. [H-3] idazoxan was inhibited by KCl in a competitive and by MnCl2 in a non-competitive way, while other cations such as Na+, Li+ and Mg2+ did not inhibit [H-3] idazoxan binding. Moreover, we investigated the regional distribution of [H-3] idazoxan and [H-3] rauwolscine along the rabbit urethra using quantitative autoradiography. Analysis of the films revealed a different distribution of these two binding sites on the urethral sections.