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The glutamate story.

ABSTRACT: Glutamatergic synaptic transmission in the mammalian central nervous system was slowly established over a period of some 20 years, dating from the 1950s. Realisation that glutamate and like amino acids (collectively known as excitatory amino acids (EAA)) mediated their excitatory actions via multiple receptors preceded establishment of these receptors as synaptic transmitter receptors. EAA receptors were initially classified as N-methyl-D-aspartate (NMDA) and non-NMDA receptors, the latter subdivided into quisqualate (later AMPA) and kainate receptors after agonists that appeared to activate these receptors preferentially, and by their sensitivity to a range of differentially acting antagonists developed progressively during the 1970s. NMDA receptors were definitively shown to be synaptic receptors on spinal neurones by the sensitivity of certain excitatory pathways in the spinal cord to a range of specific NMDA receptor antagonists. Importantly, specific NMDA receptor antagonists appeared to be less effective at synapses in higher centres. In contrast, antagonists that also blocked non-NMDA as well as NMDA receptors were almost universally effective at blocking synaptic excitation within the brain and spinal cord, establishing both the existence and ubiquity of non-NMDA synaptic receptor systems throughout the CNS. In the early 1980s, NMDA receptors were shown to be involved in several central synaptic pathways, acting in concert with non-NMDA receptors under conditions where a protracted excitatory postsynaptic potential was effected in response to intense stimulation of presynaptic fibres. Such activation of NMDA receptors together with non-NMDA receptors led to the phenomenon of long-term potentiation (LTP), associated with lasting changes in synaptic efficacy (synaptic plasticity) and considered to be an important process in memory and learning. During the 1980s, it was shown that certain glutamate receptors in the brain mediated biochemical changes that were not susceptible to NMDA or non-NMDA receptor antagonists. This dichotomy was resolved in the early 1990s by the techniques of molecular biology, which identified two families of glutamate-binding receptor proteins (ionotropic (iGlu) and metabotropic (mGlu) receptors). Development of antagonists binding to specific protein subunits is currently enabling precise identification of discrete iGlu or mGlu receptor subtypes that participate in a range of central synaptic processes, including synaptic plasticity.

SUBMITTER: Watkins JC

PROVIDER: S-EPMC1760733 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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The glutamate story.

Watkins Jeffrey C JC Jane David E DE

British journal of pharmacology 20060101

Glutamatergic synaptic transmission in the mammalian central nervous system was slowly established over a period of some 20 years, dating from the 1950s. Realisation that glutamate and like amino acids (collectively known as excitatory amino acids (EAA)) mediated their excitatory actions via multiple receptors preceded establishment of these receptors as synaptic transmitter receptors. EAA receptors were initially classified as N-methyl-D-aspartate (NMDA) and non-NMDA receptors, the latter subdi ...[more]

PMID: 16402093

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Project description:BackgroundDespite rising incidence and mortality rates in Africa, cancer has been given low priority in the research field and in healthcare services. Indeed, 57% of all new cancer cases around the world occur in low income countries exacerbated by lack of awareness, lack of preventive strategies, and increased life expectancies. Despite recent efforts devoted to cancer epidemiology, statistics on cancer rates in Africa are often dispersed across different registries. In this study our goal included identifying the most promising prevention and treatment approaches available in Africa. To do this, we collated and analyzed the incidence and fatality rates for the 10 most common and fatal cancers in 56 African countries grouped into 5 different regions (North, West, East, Central and South) over 16-years (2002-2018). We examined temporal and regional trends by investigating the most important risk factors associated to each cancer type. Data were analyzed by cancer type, African region, gender, measures of socioeconomic status and the availability of medical devices.ResultsWe observed that Northern and Southern Africa were most similar in their cancer incidences and fatality rates compared to other African regions. The most prevalent cancers are breast, bladder and liver cancers in Northern Africa; prostate, lung and colorectal cancers in Southern Africa; and esophageal and cervical cancer in East Africa. In Southern Africa, fatality rates from prostate cancer and cervical cancer have increased. In addition, these three cancers are less fatal in Northern and Southern Africa compared to other regions, which correlates with the Human Development Index and the availability of medical devices. With the exception of thyroid cancer, all other cancers have higher incidences in males than females.ConclusionOur results show that the African continent suffers from a shortage of medical equipment, research resources and epidemiological expertise. While recognizing that risk factors are interconnected, we focused on risk factors more or less specific to each cancer type. This helps identify specific preventive and therapeutic options in Africa. We see a need for implementing more accurate preventive strategies to tackle this disease as many cases are likely preventable. Opportunities exist for vaccination programs for cervical and liver cancer, genetic testing and use of new targeted therapies for breast and prostate cancer, and positive changes in lifestyle for lung, colorectal and bladder cancers. Such recommendations should be tailored for the different African regions depending on their disease profiles and specific needs.

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The glutamate story.

Publications

The glutamate story.

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