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D-Amino acids are stereoisomers of L-amino acids. They are often called unnatural amino acids, but several D-amino acids have been found in mammalian brains. Among them, D-serine is abundant in the forebrain and functions as a co-agonist of NMDA receptors to enhance neurotransmission. D-Amino-acid oxidase (DAO), which degrades neutral and basic D-amino acids, is mainly present in the hindbrain. DAO catabolizes D-serine and, therefore, modulates neurotransmission. In the brains of mutant mice and rats lacking DAO activity, the amounts of D-serine and other D-amino acids are markedly increased. Mutant mice manifested behavioral changes characteristic of altered NMDA receptor activity, likely due to increased levels of D-serine. D-Serine and DAO have been demonstrated to play important roles in cerebellar development and synaptic plasticity. They have also implicated in amyotrophic lateral sclerosis and pain response. There have also been several lines of evidence correlating DAO with schizophrenia. Taken together, the experiments indicate that D-amino acids and DAO have pivotal functions in the central nervous system.

Caffeine, a major component of coffee, exhibits pharmacological actions on the cardiovascular system. In the present study, we examined the acute effects of caffeine on blood pressure (BP) and heart rate (HR) and the influence of habitual coffee intake on cardiovascular responses to caffeine. In this double-blind, placebo-controlled study, 136 young normotensive Japanese subjects were randomized. The subjects were first divided into 84 non-habitual and 52 habitual coffee consumers and further subdivided into placebo and caffeine groups; in the placebo group they had a cup of decaffeinated coffee, whereas in the caffeine group they had a cup of caffeinated coffee. In non-habitual coffee consumers, the systolic and diastolic BP at 30, 60, and 90 min after coffee intake were significantly higher in the caffeine group than in the placebo group. However, the pressor effect of caffeine disappeared in habitual coffee consumers. The changes in HR after coffee intake were similar between the placebo and the caffeine groups in both consumers of coffee. These results suggest that a single cup of caffeinated coffee is capable of increasing BP, and that the acute pressor effect of caffeine is diminished by habitual coffee consumption.

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