RT Journal Article SR Electronic T1 Coupling of I1 Imidazoline Receptors to the cAMP Pathway: Studies with a Highly Selective Ligand, Benazoline JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1142 OP 1151 VO 57 IS 6 A1 Hugues Greney A1 Philippe Ronde A1 Céline Magnier A1 Françoise Maranca A1 Carla Rascente A1 Wilma Quaglia A1 Mario Giannella A1 Maria Pigini A1 Livio Brasili A1 Claire Lugnier A1 Pascal Bousquet A1 Monique Dontenwill YR 2000 UL http://molpharm.aspetjournals.org/content/57/6/1142.abstract AB Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to α2-adrenoceptors (α2R) and to I1 imidazoline receptors (I1R), benazoline showed a high selectivity for imidazoline receptors. Although the α2R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I1R has been reported so far. We therefore aimed to compare the effects of clonidine and benazoline on forskolin-stimulated cAMP levels in cell lines expressing either I1R only (PC12 cells), α2R only (HT29 cells), or I1R and α2R together (NG10815 cells). Clonidine proved able to decrease the forskolin-stimulated cAMP level in the cells expressing α2R and this effect could be blocked by rauwolscine. In contrast, in cells lacking these adrenoceptors, clonidine had no effect. On the other hand, benazoline and other I1receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I1R, in a rauwolscine- and pertussis toxin-insensitive manner. These effects were antagonized by clonidine. According to these results, we demonstrated that 1) α2R and I1R are definitely different entities because they are expressed independently in different cell lines; 2) α2R and I1R are both implicated in the cAMP pathway in cells (one is sensitive to pertussis toxin and the other is not); and 3) I1R might be coupled to more then one transduction pathway. These new data will be essential to further understand the physiological implications of the I1R and the functional interactions between I1 receptors and α2-adrenoceptors. The American Society for Pharmacology and Experimental Therapeutics