Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

This review considers the results of recent studies on marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, known as potent agonists of one of subtypes of glutamate receptors, the so-called kainate receptors. Novel information, particularly concerning biosynthesis, environmental roles, biological action, and syntheses of these marine metabolites, obtained mainly in last 10–15 years, is summarized. The goal of the review was not only to discuss recently obtained data, but also to provide a brief introduction to the field of marine excitatory amino acid research.

What Is the Confusion With Cortisol?

Cortisol has many roles not only in mediating the response to stress but also in the circadian rhythm, and it does so by both genomic and nongenomic cellular and molecular mechanisms. Yet, it is common to associate cortisol only with stress and, in particular, with the negative aspects of stress even though we would not survive without it. This commentary provides a brief overview not only of the diverse roles of cortisol but also of how to measure it to get meaningful information in the context of other mediators of stress and adaptation and the concepts of allostasis and allostatic load and overload. In particular, the adaptive plasticity of the brain mediated by glucocorticoids and excitatory amino acids is discussed in relation to misconceptions about what constitutes brain damage. Thus the confusion with cortisol is that it does too many important things both positive and negative!

The original description of central sensitization

The landmark study discussed in this chapter is ‘The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury’, published by Coderre and Melzack in 1992. Previous studies in this field implicate a contribution of excitatory amino acids (EAAs), specifically l-glutamate and l-aspartate, to injury-induced sensitization of nociceptive responses in the dorsal horn of the spinal cord. Repetitive stimulation of primary afferent fibres demonstrated that l-glutamate and NMDA can produce ‘wind-up’ of neuronal dorsal horn activity, and this is blocked by application of NMDA antagonists. This study uses the formalin test as a behavioural model to investigate the mechanisms underlying central sensitization and the role of EAAs, NMDA, their receptors, and their antagonists in this process.