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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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Ischemic Delayed Neuronal Death A Mitochondrial Hypothesis

TL;DR: A disturbance of mitochondrial DNA expression may be caused by dysfunction of the mitochondrial shuttle system and could cause progressive failure of energy production of CA1 neurons that eventually results in cell death.
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Neuronal nitric oxide synthase alternatively spliced forms: prominent functional localizations in the brain.

TL;DR: NOS beta, and possibly other uncharacterized splice forms, appear to be important physiological sources of NO in discrete brain regions and may account for the relatively modest level of impairment in nNOS(delta/delta) animals.
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On the specific role of the cerebellum in motor learning and cognition: Clues from PET activation and lesion studies in man

TL;DR: The cerebellar output extends even to what has been characterized as the ultimate frontal planning area, the “prefrontal” cortex, area 46, and the cerebellum may be involved in context-response linkage, and response combination even at these higher levels.
Journal ArticleDOI

Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation

TL;DR: The biology of NO and ROS in the cardiovascular system, with special emphasis on their routes of formation and regulation, are presented, as well as the therapeutic challenges and opportunities for the management of no/ROS in cardiovascular disease.
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Activity-dependent neuronal-glial and synaptic plasticity in the adult mammalian hypothalamus

TL;DR: The ultimate aim of these investigations on plasticity would be to correlate the observed structural and functional changes and to understand the way these changes are brought about by use and disuse.
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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