Title: Non‐adrenergic binding of [<sup>3</sup>H]atipamezole in rat kidney–regional distribution and comparison to α<sub>2</sub>‐adrenoceptors
Abstract: 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