The nitric oxide-cGMP system of the locus coeruleus and the hypnotic action of alpha-2 adrenergic agonists.
Dexmedetomidine (Dex), a potent, selective alpha-2 adrenergic agonist, injected bilaterally directly into the locus coeruleus (LC), 7 microgram/LC, or ip, 100 microgram/kg, produced a maximum decrease in LC cGMP (-38 and -46%, respectively). Atipamezole, a selective alpha-2 adrenergic antagonist, given into the LC, 10 microgram/LC, prevented the decrease in LC cGMP induced by Dex, given i.p. or into the LC. Dex produced a loss of righting reflex in about 80% of the animals, an effect which was prevented by pretreatment with atipamezole. The nitric oxide synthase antagonist L-Name injected bilaterally into the LC, 20 microgram/LC, produced by itself a maximum decrease in LC cGMP of 54.5%. Dex, 100 microgram/kg, ip, given after L-Name, did not further decrease LC cGMP. L-Name, by itself, did not produce a loss of righting reflex, while 6 out of 9 rats pretreated with L-Name lost their righting reflex in response to Dex. A role of the nitric oxide-cGMP system of the LC in the modulation of the hypnotic effect of alpha-2 adrenergic agonists remains uncertain.
Vulliemoz
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Y
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, USA.
Whittington
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RA
Virag
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D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D007839:Functional Laterality; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D011187:Posture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C050701:atipamezole; D009569:Nitric Oxide; D020927:Dexmedetomidine; D014446:Tyrosine 3-Monooxygenase; D006152:Cyclic GMP