Immunolocalization of Nitric Oxide Synthases at the Postsynaptic Domain of Human and Rat Neuromuscular Junctions—Light and Electron Microscopic Studies

Yang, Chih‐Chao; Alvarez, Renate B.; Engel, W. King; Haun, Charles K.; Askanas, Valerie

doi:10.1006/exnr.1997.6663

Cited by 30 publications

(26 citation statements)

References 39 publications

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“…Several studies have provided increasing evidence that most of the effects of relaxin depend on its ability to modulate the activity and/or gene expression of the various NOS isoforms (6,7,8,27,36). In this regard, numerous reports have demonstrated that the same cell type can express multiple NOS isoforms (45,39,4,13) and, by immunohistochemical and biochemical studies, it has been shown that each isoform has proper subcellular location and a potentially distinct role (24,44,20,25,43,39). However, all NOS share a common effector, e.g., NO, a diffusible gas easily crossing the cell membranes and acting at relatively long distance as an inhibitor of neurotransmission and/or muscle contraction.…”

Section: Discussionmentioning

confidence: 99%

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon

Baccari

Traini

Garella

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Baccari MC, Traini C, Garella R, Cipriani G, Vannucchi MG. Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon. Am J Physiol Endocrinol Metab 303: E1142-E1150, 2012. First published August 28, 2012 doi:10.1152/ajpendo.00260.2012.-The hormone relaxin exerts a variety of functions on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism. In the stomach and ileum, relaxin causes muscle relaxation by modulating the activity and expression of different nitric oxide synthase (NOS) isoforms region-dependently. Nothing is known on the effects of relaxin in the colon, the gut region expressing the highest number of neuronal (n) NOS␤-immunoreactive neurons and mainly involved in motor symptoms of pregnancy and menstrual cycle. Therefore, we studied the effects of relaxin exposure in the mouse proximal colon in vitro evaluating muscle mechanical activity and NOS isoform expression. The functional experiments showed that relaxin decreases muscle tone and increases amplitude of spontaneous contractions; the immunohistochemical results showed that relaxin increases nNOS␤ and endothelial (e) NOS expression in the neurons and decreases nNOS␣ and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOS␤ and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOS␣ and eNOS expression in the SMC associated with increased muscle contractility could be the consequence of continuous exposue of these cells to the NO of neuronal origin. These findings may help to better understand the physiology of NO in the gastrointestinal tract and the role that the "relaxin-NO" system plays in motor disorders such as functional bowel disease. nitric oxide synthase isoforms; nitric oxide synthase splice variants; immunohistochemistry; mechanical responses RELAXIN, a 6,000 Da hormone peptide mainly produced by the corpus luteum, has been shown to exert a variety of physiological effects on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism (1,12,17,33). The latter effects can be direct on the smooth muscle cells (SMC) or mediated by the endothelial cells (2,12,17,30,36). In the gastrointestinal tract, relaxin has been shown to cause depression of muscle contractility by modulating the activity and expression of the different nitric oxide synthase (NOS) isoforms (8,3,4,40). Interestingly, the depression of muscle contractility reported in the mouse stomach and ileum was mediated by different NOS isoforms. While in the stomach relaxin induced an increase in both the constitutive NOS isoforms, i.e., neuronal (n) NOS and endothelial (e) NOS (3, 40), in the ileum it increased the expression of eNOS and of inducible (i) NOS isoforms (8, 4). In summary, relaxin is able to act on different NOS isoforms depending on the gut...

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Section: Discussionmentioning

confidence: 99%

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon

Baccari

Traini

Garella

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Subsequent studies revealed that nNOS is associated with the complex of dystrophin-associated proteins (Chang et al, 1996;Yang et al, 1997). Evidence shows a loss of dystrophin in DMD patients and mdx mice, whose nNOS is also absent from the sarcolemma of dystrophin-deficient muscle fibers (Brenmann et al, 1995;Grozdanovic et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Administration of Chinese Herbal Medicines Facilitates the Locomotor Activity in Dystrophin-Deficient Mice

et al. 2001

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The purpose of this study was to access the effects of chinese herbal medicines on Duchenne muscular dystrophy (DMD). We use dystrophin-deficient mice (mdx), an animal model of DMD, to evaluate the effect of chinese herbal medicines on locomotor activity. The consumption of water for each mouse was controlled during the three-month experimental session. Each mouse was allowed to drink 3 ml water with or without herbal medicines daily for three months. The estimated intake of chinese herbal medicine in adult mdx mouse with 30 g weight is 100 mg/kg per day, close to a dose used in human. The locomotor activity of the mdx mice was measured every month. Monitoring the locomotor activity of mdx mice after three-month administration of chinese herbal medicines, the results showed that liu-wei-di-huang-wan (LDW) and san-lin-pai-tsu-san (SPS) can facilitate locomotor activity with the parameters of horizontal activity, total distance, number of movements, movement time, vertical activity, number of vertical movements, vertical movement time, stereotypy, number of stereotyped movements, and stereotyped movement time. These results suggest that either LDW or SPS can act as a potent herbal medicine for the pharmacological treatment of DMD patients.

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“…Synaptic actions by NO have previously been discussed in terms of retrograde muscle-to-nerve NO signaling [21]. NOS is concentrated in neuromuscular junctions of adult and developing rats, mice or humans [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

“…In the muscle fiber, NO is generated by Ca 2+ -dependent constitutively expressed NOS-1 or by one of its coexpressed muscle-specific splice variants termed NOS-Ì [14]; both are associated with the sarcolemmal dystrophin-associated glycoprotein complex (DAGC) of normal adult muscle fibers [15]. NOS-1 is concentrated at the neuromuscular junction [16][17][18] together with cyclic GMP-dependent protein kinases and soluble guanylyl cyclase [19,20] and is part of agrin-induced nicotinic acetylcholine receptor (AChR) aggregations on myotubes including NMDAreceptor, ion channels, PSD-95 or 43K-rapsyn linker proteins, suggesting fundamental signaling mechanisms of NO in neuromuscular synapse formation [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular Contacts Induce Nitric Oxide Signals in Skeletal Myotubes in vitro

Püttmann

Gerlach²,

Kruger³

et al. 2005

Neurosignals

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It has previously been shown that skeletal myotubes express nitric oxide synthase (NOS) and produce and release NO signals. NOS is also part of agrin-induced acetylcholine receptor aggregations on myotubes. As nerve-muscle interactions underlie reciprocal signaling mechanisms, we hypothesized that NO signals in target myotubes may be induced by neuromuscular contacts in development. Chimeric neuron-myotube co-cultures were prepared using p75-selected spinal cord neurons from embryonic chicken. Confocal imaging revealed robust 1,2-diaminoanthraquinone red fluorescence indicative of de novo formation of NO only in those myotubes which were contacted by neurites, also verified by pre- and postsynaptic marker costaining (anti-synaptotagmin and α-bungarotoxin). Neither soluble agrin nor sensory dorsal root ganglionic neurons showed comparable effects in this model. We concluded that in target skeletal muscle cells the NOS/NO system is controlled by motoneuron contacts by as yet incompletely understood signaling mechanisms. Endogenous NO signaling in myotubes may be essential during synapse formation and plasticity of the neuromuscular system.

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Immunolocalization of Nitric Oxide Synthases at the Postsynaptic Domain of Human and Rat Neuromuscular Junctions—Light and Electron Microscopic Studies

Cited by 30 publications

References 39 publications

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon

Administration of Chinese Herbal Medicines Facilitates the Locomotor Activity in Dystrophin-Deficient Mice

Neuromuscular Contacts Induce Nitric Oxide Signals in Skeletal Myotubes in vitro

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