Role of signal transduction in anesthetic action. α2 adrenergic agonists

M. Maze, John W Regan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The molecular mechanism for general anesthetic action is not known. The α2 adrenergic agonists represent a novel class of 'anesthetic-like' agent because of their selectivity for receptor binding sites and because the transmembrane signaling systems mediating their biologic responses in non-CNS systems are known. We have begun to characterize the signal transduction pathway involved in the anesthetic-like action of the α2 adrenergic agonists. The α2 adrenergic agonists potently decrease both central noradrenergic neurotransmission and halothane anesthetic requirements (MAC). Since MAC is only reduced by 30-40% when noradrergic neurotransmission is totally abolished and since the reduction in MAC with the highly selective α2 adrenergic agonists exceeds 90%, factors in addition to noradrenergic neurotransmission must be contributing to the anesthetic action of the α2 agonists. Studies with the superselective α2 agonist dexmedetomidine confirmed this, as the α2 agonist could still reduce the MAC for halothane in rats depleted of their central norepinephrine stores. The profound reduction in anesthetic requirements with dexmedetomidine raised the possibility that α2 adrenergic agonists may be considered an anesthetic hypnotic agent by itself. This sole anesthetic hypnotic response was established together with the confirmation that a central α2 adrenoceptor mediated this action. Subsequently, data using molecular biologic techniques suggested that the α2C4 isoreceptor was the probable receptor that mediated the anesthetic response. We further explored the postreceptor effector mechanism for the signal transduction pathway for α2 anesthestic action and identified the participation of two other molecular components, namely, a pertussis-toxin-sensitive G protein and a 4-aminopyridine-sensitive ion channel. Whether the signal transduction pathway for α2 anesthetic action mediates the further response to other non-α2 anesthetic agents needs to be defined.

Original languageEnglish (US)
Pages (from-to)409-422
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume625
StatePublished - 1991

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Signal transduction
Adrenergic Agonists
Anesthetics
Signal Transduction
Synaptic Transmission
Dexmedetomidine
Halothane
Hypnotics and Sedatives
Transduction
4-Aminopyridine
General Anesthetics
Pertussis Toxin
Ion Channels
GTP-Binding Proteins
Adrenergic Receptors
Pathway
Rats
Norepinephrine
Binding Sites

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Role of signal transduction in anesthetic action. α2 adrenergic agonists. / Maze, M.; Regan, John W.

In: Annals of the New York Academy of Sciences, Vol. 625, 1991, p. 409-422.

Research output: Contribution to journalArticle

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