[The NO/cGMP signal transduction system: a central target for anesthetics?].
The identity and physiologic function of nitric oxide (NO) as an intra- and intercellular transmitter substance have only been recognized during the last years. A variety of tissues including neuronal tissue is able to synthesize NO catalysed by the enzyme NO-synthase. Three isoforms of this enzyme have been described: the endothelial NO-synthase, the immunologic NO-synthase, and the neuronal NO-synthase. Within the cell NO binds to a haeme-moiety of the enzyme guanylyl cyclase thus increasing concentrations of cyclic guanosine monophosphate (cGMP). The NO metabolism is influenced by volatile as well as intravenous anaesthetics. The action of inhalational and intravenous anesthetics as well as other substances with hypnotic properties such as alpha 2-adrenoceptor agonists has been demonstrated to be increased after disruption of NO-synthase activity by NO-synthase inhibitors. Different mechanisms of interaction of anaesthetics with the NO/cGMP signal transduction pathway are conceivable: at the receptor level, at the NO-synthase, or at the guanylyl cyclase. Common denominator of the NO/cGMP pathway is the control of cGMP. This second messenger regulates the activity of protein kinases, phosphodiesterases, and ion channels. However, the relevance of these structures for the hypnotic-anaesthetic action of general anaesthetics is currently unclear. Recent findings in mice deficient of neuronal NO-synthase activity and in animals chronically treated with NO-synthase inhibitors suggest that in addition to the NO/cGMP-metabolism other signal transduction pathways exist that are necessary for the action of general anaesthetics.
Tonner
P H
PH
Klinik für Anästhesiologie, Universitäts-Krankenhaus Eppendorf, Hamburg. tonner@uke.uni-hamburg.de
Scholz
J
J
D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000777:Anesthetics; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006152:Cyclic GMP