British journal of pharmacology
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Opioids remain the most efficient medications against severe pain; they act on receptors that couple to heterotrimeric G-proteins in the Gαi/o family. Opioids exert many of their acute effects through modulating ion channels via Gβγ subunits. Many of their side effects are attributed to β-arrestin recruitment. Several biased agonists that do not recruit β-arrestins, but activate G-protein-dependent pathways, have recently been developed. While these compounds have been proposed to be full agonists of G-protein signalling in several high throughput pharmacological assays, their effects were not studied on ion channel targets. ⋯ TRV130, PZM21, and potentially herkinorin are partial agonists of μ receptors.
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Hydrogen sulfide donors can block the cardiovascular injury of hyperhomocysteinemia. H2 S also lowers serum homocysteine in rats with mild hyperhomocysteinemia, but the pharmacological mechanism is unknown. The present study investigated the mechanism(s) involved. ⋯ Sulfhydration or nitrosylation of CSE represents a yin/yang regulation of catalysis or binding to L-homocysteine. H2 S donor treatment enhanced CSE sulfhydration, thus lowering serum L-homocysteine, which contributed in part to the anti-atherosclerosis effects in ApoE-knockout mice with hyperhomocysteinemia.