British journal of pharmacology
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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.
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Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as IFNγ affect their levels. We have investigated this in vitro using cultures of T84 colon cancer cells. ⋯ This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
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Sphingosine-1-phosphate 2 (S1P2 ) receptors have been implicated in degranulation of mast cells. However, functions of S1P2 receptors have not been investigated in an in vivo model of allergic asthma. ⋯ Pro-allergic functions of S1P2 receptors were elucidated in a murine asthma model. S1P2 receptors were involved not only in maturation and migration of dendritic cells in the sensitization phase but also in mast cell degranulation in the challenge phase. These results suggest S1P2 receptor as a therapeutic target for allergic asthma.
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Acid-sensing ion channels (ASICs) are neuronal proton sensors emerging as potential therapeutic targets in pain of the orofacial region. Amiloride, a non-specific ASIC blocker, has been shown to exert beneficial effects in animal models of migraine and in patients. We explored the involvement of the ASIC1-subtype in cutaneous allodynia, a hallmark of migraine affecting cephalic and extra-cephalic regions in about 70% of migrainers. ⋯ These pharmacological data support the involvement of peripheral ASIC1-containing channels in migraine cutaneous allodynia as well as in its chronification. They highlight the therapeutic potential of ASIC1 inhibitors as both an acute and prophylactic treatment for migraine.
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PZM21 is a novel μ-opioid receptor ligand that has been reported to induce minimal arrestin recruitment and be devoid of the respiratory depressant effects characteristic of classical μ receptor ligands such as morphine. We have re-examined the signalling profile of PZM21 and its ability to depress respiration. ⋯ These data demonstrate that PZM21 is a low efficacy μ receptor agonist for both G protein and arrestin signalling. Contrary to a previous report, PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist.