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N-acyl amino acids and N-acyl neurotransmitter conjugates: neuromodulators and probes for new drug targets Connor M; Vaughan CW; Vandenberg RJBr J Pharmacol 2010[Aug]; 160 (8): 1857-71The myriad functions of lipids as signalling molecules is one of the most interesting fields in contemporary pharmacology, with a host of compounds recognized as mediators of communication within and between cells. The N-acyl conjugates of amino acids and neurotransmitters (NAANs) have recently come to prominence because of their potential roles in the nervous system, vasculature and the immune system. NAAN are compounds such as glycine, GABA or dopamine conjugated with long chain fatty acids. More than 70 endogenous NAAN have been reported although their physiological role remains uncertain, with various NAAN interacting with a low affinity at G protein coupled receptors (GPCR) and ion channels. Regardless of their potential physiological function, NAAN are of great interest to pharmacologists because of their potential as flexible tools to probe new sites on GPCRs, transporters and ion channels. NAANs are amphipathic molecules, with a wide variety of potential fatty acid and headgroup moieties, a combination which provides a rich source of potential ligands engaging novel binding sites and mechanisms for modulation of membrane proteins such as GPCRs, ion channels and transporters. The unique actions of subsets of NAAN on voltage-gated calcium channels and glycine transporters indicate that the wide variety of NAAN may provide a readily exploitable resource for defining new pharmacological targets. Investigation of the physiological roles and pharmacological potential of these simple lipid conjugates is in its infancy, and we believe that there is much to be learnt from their careful study.|Acylation[MESH]|Amino Acids/chemistry/metabolism/*pharmacology[MESH]|Animals[MESH]|Binding Sites[MESH]|Carrier Proteins/drug effects/metabolism[MESH]|Fatty Acids/chemistry/metabolism/*pharmacology[MESH]|Humans[MESH]|Ion Channels/drug effects/metabolism[MESH]|Ligands[MESH]|Molecular Structure[MESH]|Neurotransmitter Agents/chemistry/metabolism/*pharmacology[MESH]|Receptors, Neurotransmitter/drug effects/metabolism[MESH]|Signal Transduction/drug effects[MESH]|Structure-Activity Relationship[MESH] |
