The involvement of pertussis toxin‐sensitive G proteins in the post receptor mechanism of central I 1 ‐imidazoline receptors

To elucidate the possible involvement of pertussis toxin (PTX)‐sensitive G proteins in the post receptor mechanism of α 2 ‐adrenoceptors and imidazoline receptors, we examined the effect of pretreatment of the central nervous system with PTX on the antidysrhythmic effect of dexmedetomidine, a selective α 2 ‐adrenoceptor agonist, and rilmenidine, a selective I 1 ‐imidazoline receptor agonist on halothane‐adrenaline dysrhythmias in rats. Dexmedetomidine (0, 1.0, 2.0, 5.0 μg kg −1 min −1 , i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 μg kg −1 , i.v.) prevented the genesis of halothane‐adrenaline dysrhythmias in a dose‐dependent fashion. Both idazoxan (10, 20 μg kg −1 , intracerebroventricularly (i.c.v.)), an α 2 ‐adrenoceptor antagonist with high affinity for imidazoline receptors, and rauwolscine, (40 μg kg −1 , i.c.v.), an α 2 ‐adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 μg kg −1 min −1 , i.v.), but the inhibitory potency of idazoxan was much greater than that of rauwolscine. While the pretreatment with PTX (0.1, 0.5, 1.0 μg kg −1 , i.c.v.) did not change the dysrhythmogenecity of adrenaline, this treatment completely blocked the antidysrhythmic property of rilmenidine (20 μg kg −1 , i.v.) as well as dexmedetomidine (5.0 μg kg −1 min −1 , i.v.). It is suggested that central I 1 ‐imidazoline receptors as well as α 2 ‐adrenoceptors may be functionally coupled to PTX‐sensitive G proteins.British Journal of Pharmacology (1997) 120 , 1575–1581; doi: 10.1038/sj.bjp.0701090