Cellular and pharmacological studies for protection ofneuronal and endothelial cells

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We investigated the pharmacological and biochemical mechanisms of neuronal and endothelial cells functions in the present study. The results were : 1) In PC12 cells, 1,2,3,4-tetrahydroisoquinoline, an endogenous neurotoxin for dopaminergic neurons, caused the delayed cell death. The mRNAs of IL6 and cytosolic phospholipase A2 levels in PCI2 cells were regulated by TIQ treatment 2) S-Nitroso-cysteine, a stable and endogenous NO compound, is incorporated by the L-type amino acid transporter in PC 12 cells. The effects of S-nitroso-cysteine appeared to be mediated by S-nitrosylation of functional proteins such as cytosolic phospholipase A2 and Ca2+-channels in PC 12 cells. The effects of S-nitroso-cysteine were inhibited by specific amino acids such as L-leucine. 3) Secretory type of phospholipase A2 is expressed in neuronal cells, and the activity was regulated by the SH group-reactive agents such as phenylarsine oxide. The activity of secretory phospholipase A2 in membrane may be regula … More ted by the membrane-associated and redox-level regulating proteins such as protein disulfide isomerase. 4) Inhibition of superoxise dismutase caused an increase of arachidonic acid release and mRNA and protein levels of cytosolic phospholipase A2 in PC12 cells. Several ceramide analogs and sphyngosine-1-phosphate analogs regulated arachidonic acid metabolism in neuronal cells. 5) Activation of vanilloid receptor 1 by the central injection of capsaicin and anandamide and the activation of opioid receptor-like 1 (ORL1) receptor by nociceptin caused gastric acid secretion through mechanisms involving the vagus nerve in rats. Activation of kappa-opioid receptor system in the CNS coupled with glutamate and gamma-amino butyric acid receptor systems in the CNS, and thus stimulated gastric acid secretion in rats. 6) Aconite alkaloids such as mesaconitine showed activation of Ca2+ influx and NO synthase and thus caused relaxation in rat aorta. In rat small artery, Ca2+ influx induced by mesaconitine caused relaxation via the production of endothelium-derived hyperpolarizing factor. Mitragynine-related indole alkaloids showed the opioid agonistic activities, and the OH-group in the 7-position was important for the activation of opioid receptors. Less