THE INVOLVEMENT OF PERTUSSIS-TOXIN-SENSITIVE G-PROTEINS IN THE POST RECEPTOR MECHANISM OF CENTRAL I-1-IMIDAZOLINE RECEPTORS

1 To elucidate the possible involvement of pertussis toxin (PTX)-sensi tive G proteins in the post receptor mechanism of alpha(2)-adrenocepto rs and imidazoline receptors, we examined the effect of pretreatment o f the central nervous system with PTX on the antidysrhythmic effect of dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, and rilme nidine, a selective I-1-imidazoline receptor agonist on halothane-adre naline dysrhythmias in rats. 2 Dexmedetomidine (0, 1.0, 2.0, 5.0 mu g kg(-1) min(-1), i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 mu g kg(-1) , i.v.) prevented the genesis of halothane-adrenaline dysrhythmias in a dose-dependent fashion. Both idazoxan (10, 20 mu g kg(-1), intracere broventricularly (i.c.v.)), an alpha(2)-adrenoceptor antagonist with h igh affinity for imidazoline receptors, and rauwolscine, (40 mu g kg(- 1), i.c.v.), an alpha(2)-adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 mu g kg(-1) min(-1), i.v.), but the inhibitory potency of idazoxan was m uch greater than that of rauwolscine. While the pretreatment with PTX (0.1, 0.5, 1.0 mu g kg(-1) i.c.v.) did not change the dysrhythmogeneci ty of adrenaline, this treatment completely blocked the antidysrhythmi c property of rilmenidine (20 mu g kg(-1), i.v.) as well as dexmedetom idine (5.0 mu g kg(-1) min(-1), i.v.). 3 It is suggested that central I-1-imidazoline receptors as well as alpha(2)-adrenoceptors may be fun ctionally coupled to PTX-sensitive G proteins.