Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain

John Garthwaite, Sarah L. Charles, Russell Chess-Williams

Research output: Contribution to journalLetterResearchpeer-review

2157 Citations (Scopus)

Abstract

In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels1-3. It has been known for many years that in the central nervous system (CNS) the excitatory neurotran-smitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low4. Recent evidence indicates that cell-cell interactions are involved in this response5. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-depen-dent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells.

Original languageEnglish
Pages (from-to)385-388
Number of pages4
JournalNature
Volume336
Issue number6197
DOIs
Publication statusPublished - 1 Jan 1988
Externally publishedYes

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Neurology
Brain
Chemical activation
Hormones
Endothelial cells
Muscle
Neuroglia
Bradykinin
Cyclic GMP

Cite this

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title = "Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain",
abstract = "In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels1-3. It has been known for many years that in the central nervous system (CNS) the excitatory neurotran-smitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low4. Recent evidence indicates that cell-cell interactions are involved in this response5. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-depen-dent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells.",
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Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. / Garthwaite, John; Charles, Sarah L.; Chess-Williams, Russell.

In: Nature, Vol. 336, No. 6197, 01.01.1988, p. 385-388.

Research output: Contribution to journalLetterResearchpeer-review

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AU - Charles, Sarah L.

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N2 - In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels1-3. It has been known for many years that in the central nervous system (CNS) the excitatory neurotran-smitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low4. Recent evidence indicates that cell-cell interactions are involved in this response5. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-depen-dent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells.

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