Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital.
Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors, produces a hypnotic-anesthetic action in rats. The mechanism for this response may involve an inhibitory G-protein and increased conductance through a potassium channel. To investigate this, the effects of pertussis toxin, a specific inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in rats. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. To preclude the possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic-anesthetic action of dexmedetomidine via indirect central nervous system excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic-anesthetic action of pentobarbital also were assessed. Pentobarbital-induced hypnosis was not attenuated by either treatment. These results suggest that the receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine involves an inhibitory G-protein and increased conductance through a potassium channel.
Doze
V A
VA
Department of Anesthesia, Stanford University School of Medicine, California.
Chen
B X
BX
Tinklenberg
J A
JA
Segal
I S
IS
Maze
M
M
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D010424:Pentobarbital / Q000494:pharmacology*; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D015761:4-Aminopyridine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D010424:Pentobarbital; D020926:Medetomidine