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Hydrogen sulfide:from the smell of the past of the past to the mediator of the future

MOORE P.K

Pharmaceutical Science Division,Franklin Wilkins Building,King’s College,University of London,London SEl 9NH,UK

摘要:<正>The last two decades has witnessed considerable interest in the physiology of naturally occurring gases starting with nitric oxide(NO)and carbon monoxide(CO)and progressing,in more recent years,to hydrogen sulfide(H2S).H2S has now evolved into a biologically active mediator in its own right and novel drugs which mimic its effects or alter its biosynthesis are beginning to be developed as potential therapeutics.H2S is formed from Lcysteine in mammalian cells mainly by the activity of two pyridoxal phosphate-dependent enzymes,cystathionineγlyase(CSE)and cystathionineβsynthetase(CBS).Other enzymatic(or even chemical)reactions may also form H2S naturally.Despite much work,the precise physiological significance of H2S remains controversial.For example, H2S dilates blood vessels in vitro and in vivo most probably by opening vascular KATPchannels.However,effects on other mechanisms such as intracellular pH or Ca2+flux may also play a part in the dilator effect of this gas. Furthermore,some blood vessels will contract(not dilate)in response to H2S.The precise role of H2S in inflammation is also far from clear with both pro-and anti-inflammatory effects of this gas reported in the literature.The part played by H2S in the nervous system is yet to be resolved.Deranged biosynthesis of H2S is a feature of animal models of stroke and perhaps also in Alzheimer’s disease in man.However,the biological effects of H2S in neurodegeneration are complex with some reports suggesting that H2S triggers primary cortical neurone death via glutamate receptor activation whilst others suggest that this gas is neuroprotective.The situation is somewhat similar in terms of pain perception with both hyperalgesic and analgesic effects of this gas described.Great progress has been made in the last several years and we now have a much clearer picture of the biological significance of H2S.However,many questions still need to be answered.What are the natural ’triggers’ for H2S production in different cells? How much H2S is formed locally in the cell environment?How,and at what levels,does H2S interact with NO and CO?How do we explain the often contradictory effects of this gas in the cardiovascular and nervous systems?It is to be hoped that the next few years will provide answers to some of these questions.It is to be expected that the next few years will also raise many more questions to be addressed.
会议名称:

2008北京国际生理科学学术大会

会议时间:

2008-10

会议地点:

中国北京

  • 专辑:

    医药卫生科技

  • 专题:

    基础医学

  • 分类号:

    R341

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