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

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.

The Immp2l mutation causes age‐dependent degeneration of cerebellar granule neurons prevented by antioxidant treatment

“…Physiological levels of nitric oxide are necessary for the survival of differentiated cerebellar granule cells (Ciani et al ., 2002). nNOS is highly expressed in cerebellar granule neurons (Bredt et al ., 1990; Bredt & Snyder, 1992). We previously reported that −/− mice show erectile dysfunction and decreased hypothalamic cGMP level (Lu et al ., 2008; Han et al ., 2013), both could result from negation of nitric oxide by mitochondrial superoxide.…”

Effect of Nitric Oxide Blockade by NG-Nitro-l-Arginine on Cerebral Blood Flow Response to Changes in Carbon Dioxide Tension

“…Recent studies suggest that endo thelium-derived factors are not involved as damage of the endothelium in vitro or in vivo was found not to influence the central vasodilator response to CO2 (Gotoh et al, 1987;Toda et al, 1989). However, the pioneering work of Bredt et al (1990) has demon strated NO synthase immunoreactivity in neurons and also in perivascular nerves contacting smooth muscles (but not in the smooth muscle cells). An astrocyte-derived vasorelaxing factor with similar properties to those of NO has also been described (Murphy et al, 1990).…”

Theoretical aspects of sensory substitution and of neurotransmission-related reorganization in spinal cord injury

“…5,42 Many functions may be produced by combinations of both types of neurotransmission. In the piano playing example presented above, in addition to the relevant synaptic mechanisms, the ®nger movements can be more precise in the presence of adequate preparation including changes in brain tone (probably mediated by noradrenaline), and the visual perception of the tennis game may require neuronal receptivity to be set at a high level, probably involving several neurotransmitters, including nitric oxide 50 and dopamine 51 in the retina, serotonin and histamine in the lateral geniculate nucleus 52,53 and noradrenaline in the visual cortex. 54 These e ects appear to be primarily non-synaptically mediated.…”