Non‐adrenergic binding of [ 3 H]atipamezole in rat kidney–regional distribution and comparison to α 2 ‐adrenoceptors

Atipamezole (4‐(2‐ethyl‐2,3‐dihydro‐1H‐inden‐2‐yl)‐1H‐imidazole) was first introduced as a potent and specific α 2 ‐adrenoceptor antagonist, but in some tissues [ 3 H]atipamezole identifies an additional population of binding sites, distinct from both classical α 2 ‐adrenoceptors and I 1 ‐ and I 2 ‐imidazoline receptors identified with [ 3 H] para ‐aminoclonidine or [ 3 H]idazoxan. In the present study we have characterized [ 3 H]atipamezole binding sites in rat kidney by receptor autoradiography and membrane binding assays and determined whether they are pharmacologically identical with the previously described binding sites for [ 3 H] para ‐aminoclonidine and [ 3 H]idazoxan. [ 3 H]RX821002 and [ 3 H]rauwolscine were used to compare the regional distribution of α 2 ‐adrenoceptors to that of non‐adrenergic binding sites of [ 3 H]atipamezole. Comparative autoradiographic experiments demonstrated the differential localisation of [ 3 H]atipamezole, [ 3 H]RX821002 and [ 3 H]rauwolscine binding sites in rat kidney. The pattern of distribution of non‐adrenergic [ 3 H]atipamezole binding sites is clearly distinct from that of α 2 ‐adrenoceptors. The non‐adrenergic binding of [ 3 H]atipamezole in rat kidney does not fall into any of the previously identified three classes of imidazoline receptors studied with [ 3 H] para ‐aminoclonidine, [ 3 H]idazoxan and [ 3 H]RX821002. Atipamezole had no inhibitory effect on MAO‐A or MAO‐B activity in renal membranes, which speaks against the involvement of MAOs in the observed radioligand binding.British Journal of Pharmacology (1999) 128 , 1215–1222; doi: 10.1038/sj.bjp.0702917