Abstract

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.