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Journal ArticleDOI

Localization of nitric oxide synthase indicating a neural role for nitric oxide

David S. Bredt, +2 more
- 25 Oct 1990 - 
- Vol. 347, Iss: 6295, pp 768-770
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TLDR
It is demonstrated that NO synthase in the brain to be exclusively associated with discrete neuronal populations, and prominent neural localizations provided the first conclusive evidence for a strong association of NO with neurons.
Abstract
Nitric oxide (NO), apparently identical to endothelium-derived relaxing factor in blood vessels, is also formed by cytotoxic macrophages, in adrenal gland and in brain tissue, where it mediates the stimulation by glutamate of cyclic GMP formation in the cerebellum Stimulation of intestinal or anococcygeal nerves liberates NO, and the resultant muscle relaxation is blocked by arginine derivatives that inhibit NO synthesis It is, however, unclear whether in brain or intestine, NO released following nerve stimulation is formed in neurons, glia, fibroblasts, muscle or blood cells, all of which occur in proximity to neurons and so could account for effects of nerve stimulation on cGMP and muscle tone We have now localized NO synthase protein immunohistochemically in the rat using antisera to the purified enzyme We demonstrate NO synthase in the brain to be exclusively associated with discrete neuronal populations NO synthase is also concentrated in the neural innervation of the posterior pituitary, in autonomic nerve fibres in the retina, in cell bodies and nerve fibres in the myenteric plexus of the intestine, in adrenal medulla, and in vascular endothelial cells These prominent neural localizations provide the first conclusive evidence for a strong association of NO with neurons

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Citations
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Nitric oxide: a physiologic mediator of penile erection

TL;DR: No is established as a physiologic mediator of erectile function and small doses of NO synthase inhibitors abolished electrophysiologically induced penile erections.
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A requirement for the intercellular messenger nitric oxide in long-term potentiation

TL;DR: Findings suggest that nitric oxide liberated from postsynaptic neurons may travel back to presynaptic terminals to cause LTP expression.
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Chronic infections and inflammatory processes as cancer risk factors : possible role of nitric oxide in carcinogenesis

TL;DR: Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development.
Journal ArticleDOI

Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures

TL;DR: Immunohistochemical localization of NOS in cultures and intact brain demonstrates widespread distribution of the cell processes suggesting that NOS neurons contact the majority of cortical neurons and so could mediate widespread neurotoxicity.
Journal ArticleDOI

Gases as biological messengers: nitric oxide and carbon monoxide in the brain

TL;DR: The involvement of NO and CO in several important aspects of neuronal function suggests that agents affecting the synthesis, transactions, and disposition of these gases are bound to have clinical relevance.
References
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Journal ArticleDOI

Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.

TL;DR: It is shown that nitric oxide synthetase activity requires calmodulin, and the native enzyme appears to be a monomer.

Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme (endothelium-derived relaxing factor/arginine/cGMP)

TL;DR: In this paper, it was shown that NO synthetase is a calmodulin-requiring enzyme, and showed that NO formation is accompanied by the stoichiometric conversion of arginine to citrulline.
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Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain.

TL;DR: It is reported 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 that accounts for the cGMP responses that take place following NMDA receptor activation.
Journal ArticleDOI

Endothelium-derived relaxing and contracting factors.

TL;DR: Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels as mentioned in this paper.
Journal ArticleDOI

Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum

TL;DR: It is established that nitric oxide mediates the stimulation by glutamate of cGMP formation, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes.
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