Effects of general anaesthetics on second messenger systems

This paper focuses on the potential role of second messenger systems as general anaesthetic targets. Intracellular free calcium, cyclic nucleotides (cAMP, cGMP), inositol polyphosphates, the protein kinase-activating second messenger diacylglycerol, and the transducing G proteins involved in receptor-coupled second messenger pathways have important functions in the neurone that make them promising candidates for sites of relevant anaesthetic actions. To date, however, only distinct members of the heterogeneous family of voltage-operated Ca2+ channels (T and certain sensitive L type channels) and particularly Ca2+ permeable ligand-activated receptor channels, such as the nicotinic acetycholine receptor or the N-methyl-D-aspartate receptor, have been identified as sensitive to the action of general anaesthetics (volatile anaesthetics, barbiturates, ketamine). Conflicting results have been reported on interactions of general anaesthetics with G proteins and their respective second messenger systems. Thus, based on the little work done so far, the receptor-coupled second messengers cannot be considered very convincing candidates for anaesthetic sites. Nevertheless, they remain a challenging area for future research.