Non‐adrenergic binding of [³H]atipamezole in rat kidney–regional distribution and comparison to α₂‐adrenoceptors

Abstract

Atipamezole (4‐(2‐ethyl‐2,3‐dihydro‐1H‐inden‐2‐yl)‐1H‐imidazole) was first introduced as a potent and specific α2‐adrenoceptor antagonist, but in some tissues [3H]atipamezole identifies an additional population of binding sites, distinct from both classical α2‐adrenoceptors and I1‐ and I2‐imidazoline receptors identified with [3H]para‐aminoclonidine or [3H]idazoxan. In the present study we have characterized [3H]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 [3H]para‐aminoclonidine and [3H]idazoxan. [3H]RX821002 and [3H]rauwolscine were used to compare the regional distribution of α2‐adrenoceptors to that of non‐adrenergic binding sites of [3H]atipamezole. Comparative autoradiographic experiments demonstrated the differential localisation of [3H]atipamezole, [3H]RX821002 and [3H]rauwolscine binding sites in rat kidney. The pattern of distribution of non‐adrenergic [3H]atipamezole binding sites is clearly distinct from that of α2‐adrenoceptors. The non‐adrenergic binding of [3H]atipamezole in rat kidney does not fall into any of the previously identified three classes of imidazoline receptors studied with [3H]para‐aminoclonidine, [3H]idazoxan and [3H]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:

RX 821002 as a Tool for Physiological Investigation of α2‐Adrenoceptors

“…It labels only a single population of á 2 -adrenoceptors in guinea pig kidney, which is known to contain both main types of imidazoline receptor (111). Atipamezole, on the other hand, does have an imidazoline structure, and binds with moderate affinity (40 nM) to non-adrenergic binding sites in rat lung and kidney that are distinct from I 1 , I 2 , or I 3 receptors (98,99). It can also displace dexmedetomidine from non-adrenergic sites in rat spinal cord (97), which are again distinct from the characterized imidazoline receptors.…”

Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects

“…The renal effects of these drugs are probably not entirely mediated by their central sympatholytic action (37). Peripheral renal targets may mediate the renal response to these drugs, such as 1) a heterogeneous population of imidazoline receptors (10,35), 2) renal ␣ 2 -adrenoceptor mediated NO release (45), 3) atrial natriuretic peptide (28), and 4) vasopressin (38).…”

Upregulation of Gastric Norepinephrine With β-Adrenoceptors and Gastric Dysmotility in a Rat Model of Functional Dyspepsia

“…Canciani et al (2006) investigated the intragastric pressure by in vivo balloon measurement, whereas our studies were carried out on freshly isolated gastric muscle strips via an ex vivo force transducer. Moreover, the expression of α 2 -adrenoceptors has been reported to be widely distributed in the brain and myenteric plexus (Sjoholm et al 1999), indicating that α 2 -adrenoceptors are mainly involved in the regulation of gastric motility via the neural pathway.…”