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The involvement of pertussis toxin‐sensitive G proteins in the post receptor mechanism of central I 1 ‐imidazoline receptors
Author(s) -
Takada Koji,
Hayashi Yukio,
Kamibayashi Takahiko,
Mammoto Tadanori,
Yamatodani Atsushi,
Kitamura Seiji,
Yoshiya Ikuto
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701090
Subject(s) - imidazoline receptor , idazoxan , rauwolscine , rilmenidine , agmatine , pertussis toxin , chemistry , agonist , pharmacology , receptor , endocrinology , antagonist , mechanism of action , dexmedetomidine , medicine , moxonidine , g protein , yohimbine , biology , biochemistry , prazosin , arginine , amino acid , sedation , in vitro
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