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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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Journal ArticleDOI

Paraventricular nucleus of the hypothalamus and elevated sympathetic activity in heart failure: the altered inhibitory mechanisms

TL;DR: Reduced inhibitory actions of NO and/or GABA within the PVN may exaggerate an increase in the actions of excitatory neurotransmitters such as glutamate and angiotensin II withinThe PVN and this may contribute to the overall sympatho-excitation commonly observed in HF.
Journal ArticleDOI

Urinary bladder-urethral sphincter dysfunction in mice with targeted disruption of neuronal nitric oxide synthase models idiopathic voiding disorders in humans

TL;DR: Bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase are described which model the clinical disorders ofiopathic voiding disorders.
Journal ArticleDOI

Immobilization-induced stress activates neuronal nitric oxide synthase (nNOS) mRNA and protein in hypothalamic-pituitary-adrenal axis in rats.

TL;DR: The present findings suggest that psychological and/or physiological stress causes NO release in hypothalamic-pituitary-adrenal (HPA) axis and in sympatho-ad Renal system and it is suggested that NO may modulate a stress-induced activation of the HPA axis and the sympatho’s medullary system.
Journal ArticleDOI

Nitric oxide-dependent efflux of cGMP in rat cerebellar cortex: an in vivo microdialysis study

TL;DR: In this article, the authors used intracerebellar microdialysis in awake, freely moving rats to test the hypothesis that activation of nitric oxide synthase in the cerebellar cortex results in the release of cGMP.
Journal ArticleDOI

Nitric oxide control of steroidogenesis: endocrine effects of NG-nitro-L-arginine and comparisons to alcohol.

TL;DR: Results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.
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.
Journal ArticleDOI

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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