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

In the present study, pharmacological and biochemical binding characteristics of [H-3]idazoxan, an originally thought alpha-2-adrenoceptor antagonist, have been determined in smooth muscle of rabbit urethra. It is shown that [H-3]idazoxan labels with high affinity non-adrenergic binding sites. Specific binding of [H-3]idazoxan is inhibited by compounds possessing an imidazoline or a guanidinium moiety whereas phenylethanolamines and classical alpha-2-antagonists are ineffective competitors which suggests an imidazoline-preferring binding site. However, imidazolidines such as clonidine and p-aminoclonidine are poorly effective, which differs considerably from pharmacological characteristics of imidazoline binding sites previously reported in the central nervous system. In addition, it is shown that K+ and Mn2+ inhibit [H-3]idazoxan binding in a competitive and non-competitive manner, respectively. Other cations such as Na+, Li+ and Mg2+ have no significant effect. It is shown that K+ accelerates the dissociation of [H-3]idazoxan binding while Mn2+ does not produce any modification. These results suggest that K+ may bind to an allosteric site, while Mn2+ may bind with a membrane component susceptible to alter [H-3]idazoxan binding sites.