The involvement of pertussis toxin-sensitive G proteins in the post receptor mechanism of central I1-imidazoline receptors.
1. To elucidate the possible involvement of pertussis toxin (PTX)-sensitive G proteins in the post receptor mechanism of alpha 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 alpha 2-adrenoceptor agonist, and rilmenidine, a selective I1-imidazoline receptor agonist on halothane-adrenaline dysrhythmias in rats. 2. Dexmedetomidine (0, 1.0, 2.0, 5.0 micrograms kg-1 min-1.i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 micrograms kg-1, i.v.) prevented the genesis of halothane-adrenaline dysrhythmias in a dose-dependent fashion. Both idazoxan (10, 20 micrograms kg-1, intracerebroventricularly (i.c.v.)), an alpha 2-adrenoceptor antagonist with high affinity for imidazoline receptors, and rauwolscine, (40 micrograms kg-1, i.c.v.), an alpha 2-adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 micrograms 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 micrograms kg-1, i.c.v.) did not change the dysrhythmogenecity of adrenaline, this treatment completely blocked the antidysrhythmic property of rilmenidine (20 micrograms kg-1, i.v.) as well as dexmedetomidine (5.0 micrograms kg-1 min-1, i.v.). 3. It is suggested that central I1-imidazoline receptors as well as alpha 2-adrenoceptors may be functionally coupled to PTX-sensitive G proteins.
Takada
K
K
Department of Anesthesiology, Osaka Medical Center & Research Institute for Maternal & Child Health, Japan.
Hayashi
Y
Y
Kamibayashi
T
T
Mammoto
T
T
Yamatodani
A
A
Kitamura
S
S
Yoshiya
I
I
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D020926:Medetomidine; D010080:Oxazoles / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000077769:Rilmenidine; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D020926:Medetomidine; D000077769:Rilmenidine