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Z Grozdanovic

Publications and source records attributed to Z Grozdanovic.

At least 19 recordsLinked to original sources
PubMed2001

NO message from muscle.

The synthesis of the free radical gas nitric oxide (NO) is catalyzed by the enzyme NO synthase (NOS). NOS converts arginine and molecular oxygen to NO and citrulline in a reaction that requires NADPH, FAD, FMN, and tetrahydrobiopterin as cofactors. Three types of NOS have been identified by molecular cloning. The activity of the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) is Ca(2+)/calmodulin-dependent, whereas that the inducible NOS (iNOS) is Ca(2+)-insensitive. The predominant NOS isoform in skeletal muscle is nNOS. It is present at the sarcolemma of both extra- and intrafusal muscle fibers. An accentuated accumulation of nNOS is found in the endplate area. This strict sarcolemmal localization of nNOS is due its association with the dystrophin-glycoprotein complex, which is mediated by the syntrophins. The activity of nNOS in skeletal muscle is regulated by developmental, myogenic, and neurogenic influences. NO exerts several distinct effects on various aspects of skeletal muscle function, such as excitation-contraction coupling, mitochondrial energy production, glucose metabolism, and autoregulation of blood flow. Inside the striated muscle fibers, NO interacts directly with several classes of proteins, such as soluble guanylate cyclase, ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, glyceraldehyde-3-phosphate dehydrogenase, and mitochondrial respiratory chain complexes, as well as radical oxygen species. In addition, NO produced and released by contracting muscle fibers diffuses to nearby arterioles where it acts to inhibit reflex sympathetic vasoconstriction.

Animals↗
PubMed2001

Expression of Leu-19 (CD56, N-CAM) and nitric oxide synthase (NOS) I in denervated and reinnervated human skeletal muscle.

Neural cell adhesion molecule (N-CAM, Leu-19, CD 56) expression appears during muscle fiber regeneration and after denervation. Sarcolemma-associated nitric oxide synthase (NOS) I, however, disappears from denervated myofibers. The dynamics of expression of both proteins were studied in 5 cases of acute/subacute denervation, 28 cases of chronic denervation with and without collateral reinnervation, 5 cases of the intermediate type spinal muscular atrophy (SMA 2), and in 2 normal biopsies. NOS I and its NADPH diaphorase (NADPHd) activity disappeared from the sarcolemma region shortly after denervation, and before the appearance of denervation atrophy. N-CAM was found diffusely distributed in the sarcoplasm at the most severe phase of denervation atrophy in the majority of highly atrophic fibers. During reinnervation, NOS I expression remained absent and in part of the cases the target/targetoid phenomenon appeared. In parallel with the increase in volume of the reinnervated muscle fibers, the intensity of N-CAM immunoreactivity decreased progressively. After full restitution of muscle fiber caliber, the target/targetoid phenomenon and N-CAM immunostaining disappeared completely, and, finally, NOS I reappeared in the sarcolemma region. The sarcolemmal expression of dystrophin and dystrophin-associated proteins was unchanged during denervation. NOS I was completely absent in children with SMA 2, since the protein does not appear before 5 years of age in skeletal muscle, while N-CAM was very intensely expressed in the sarcoplasm of highly atrophic denervated muscle fibers. In conclusion, this study suggests that innervation is an important factor for selective gene expression and positioning of NOS I and N-CAM in skeletal muscle and gives practical information for the assessment of the phase and developmental stage of the denervation and reinnervation process.

CD56 Antigen↗
PubMed1999

Comparative localization of heme oxygenase-2 and nitric oxide synthase in the autonomic innervation to the human ductus deferens and seminal vesicle.

PURPOSE: The aim of present study was to determine the topographic relationship between heme oxygenase-2 (HO-2), which synthesizes carbon monoxide (CO), and neuronal nitric oxide synthase (nNOS), which generates nitric oxide (NO), in the autonomic nerves of the human ductus deferens and seminal vesicle. MATERIALS AND METHODS: Specimens of the ductus deferens and seminal vesicle were obtained during cancer surgery or vasectomy. HO-2 and nNOS were localized by indirect immunofluorescence. Additionally, the histochemical NADPH-diaphorase (NADPH-d) activity of NOS was demonstrated using a standard staining method and some modifications. RESULTS: Anti-HO-2 labeling stained virtually all nerve cell bodies in local ganglia of the pelvic plexus, which is composed of a mixed population of postganglionic sympathetic and parasympathetic neurons supplying the pelvic viscera. Furthermore, nerve cell bodies in the wall of the seminal vesicle, which are considered an extension of the pelvic plexus, were also found to stain positively for HO-2. Some of the HO-2-immunoreactive ganglion cells were also nNOS-positive, their proportion varying between individual ganglia but generally not exceeding 20%. Both enzymes were present in large adventitial nerve trunks. Only nNOS but no HO-2 was found in small intramuscular and mucosal nerve fibers. In both the ductus deferens and seminal vesicle, the highest density of nNOS-containing nerve fibers was in the lamina propria of the mucosa. A well-developed plexus of nNOS-positive nerve fibers was also observed in the muscular layer of the seminal vesicle. By contrast, there was a very sparse innervation by nNOS-positive nerve fibers in the muscle coat of the ductus deferens. In addition, a population of epithelial cells in the seminal vesicle may contain an isoform of NOS, as revealed by a resistant NADPH-d activity. CONCLUSIONS: These findings set the scene for functional studies which will hopefully clarify the biological role of CO and NO in the control of the ductus deferens and seminal vesicle.

Aged↗
PubMed1999

Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin-glycoprotein complex.

The present review deals with the anatomical distribution, physiological importance, and pathological implications of the neuronal-type nitric oxide synthase (nNOS) in skeletal muscle. Throughout the body, nNOS is located beneath the sarcolemma of skeletal muscle fibers. In rodents, nNOS is enriched in type IIb muscle fibers, but is more homogenously distributed among type II and type I fibers in humans and subhuman primates. It is accumulated on the postsynaptic membrane at the neuromuscular junction. An increased concentration of nNOS is noted at the sarcolemma of muscle spindle fibers, in particular nuclear bag fibers, which belong to type I fibers. The association of nNOS with the sarcolemma is mediated by the dystrophin-glycoprotein complex. Specifically, nNOS is linked to alpha 1-syntrophin through PDZ domain interactions. Possibly, it also directly binds to dystrophin. The activity and expression of nNOS are regulated by both myogenic and neurogenic factors. Besides acetylcholine, glutamate has also been shown to stimulate nNOS, probably acting through N-methyl-D-aspartate receptors, which are colocalized with nNOS at the junctional sarcolemma. Functional studies have implicated nitric oxide as a modulator of skeletal muscle contractility, mitochondrial respiration, carbohydrate metabolism, and neuromuscular transmission. A clinically relevant aspect of nNOS is its absence from the skeletal muscle sarcolemma of patients with Duchenne muscular dystrophy (DMD). A concept is presented which suggests that, as a consequence of the disruption of the dystrophin-glyoprotein complex in DMD, nNOS fails to become attached to the sarcolemma and is subject to downregulation in the cytosol.

Animals↗
PubMed1998

Co-localization of nitric oxide synthase I (NOS I) and NMDA receptor subunit 1 (NMDAR-1) at the neuromuscular junction in rat and mouse skeletal muscle.

Nitric oxide synthase I (NOS I) has been localized to the skeletal muscle sarcolemma in a variety of vertebrate species including man. It is particularly enriched at neuromuscular junctions. Recently, the N-methyl-D-aspartate (NMDA) receptor subunit 1 (NMDAR-1) has been detected in the postjunctional sarcolemma of rat diaphragm, providing a clue as to the possible source of Ca2+ ions that are necessary for NOS I activation. To address this possibility, we studied the distribution of NMDAR-1 and NOS I in mouse and rat skeletal muscles by immunohistochemistry and enzyme histochemistry. NMDAR-1 and NOS I were closely associated at neuromuscular junctions primarily of type II muscle fibers. NOS I was also present in the extrajunctional sarcolemma of this fiber type. Dystrophin, beta-dystroglycan, alpha-sarcoglycan, and spectrin were found normally expressed in both the junctional and extrajunctional sarcolemma of both fiber types. By contrast, in the muscle sarcolemma of MDX mice, dystrophin and dystrophin-associated proteins were reduced or absent. NOS I immunoreactivity was lost from the extrajunctional sarcolemma and barely detectable in the junctional sarcolemma. NOS I activity was clearly demonstrable in the junctional sarcolemma by NADPH diaphorase histochemistry, especially when the two-step method was used. NMDAR-1 was not altered. These data suggest that different mechanisms act to attach NOS I to the junctional versus extrajunctional sarcolemma. It may further be postulated that NMDA receptors are involved not only in the regulation but also sarcolemmal targeting of NOS I at neuromuscular junctions of type II fibers. The evidence that glutamate may function as a messenger molecule at vertebrate neuromuscular junction is discussed.

Animals↗
PubMed1998

Role of serotonin in obsessive-compulsive disorder.

BACKGROUND: Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRIs). METHOD: The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour. RESULTS: In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities. CONCLUSIONS: We hypothesise that continuous treatment with SSRIs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Biogenic Monoamines↗
PubMed1997

Differences in the localization of the postsynaptic nitric oxide synthase I and acetylcholinesterase suggest a heterogeneity of neuromuscular junctions in rat and mouse skeletal muscles.

Recently, nitric oxide synthase (NOS) I has been identified in skeletal muscle fibers, where the enzyme is found to be associated to the sarcolemma by the alpha 1-syntrophin-dystrophin complex. It has, however, been proposed that a substantial proportion of NOS I at the neuromuscular junction (NMJ) is of neuronal origin. We have, therefore, investigated the distribution of NOS I in NMJ of normal rats and mice as well as mdx mice which lack dystrophin and, consequently, NOS I in the sarcolemma region by enzyme histochemical and immunohistochemical techniques. Sites of NOS I accumulation, evident at NMJ of healthy animals, were absent in mdx mice, indicating a predominantly, if not exclusively, postsynaptic localization of NOS I at NMJ. Moreover, simultaneous demonstration of acetylcholinesterase (AChE) activity revealed a heterogeneity of NMJ in rat and mouse skeletal muscles: type I showed only AChE activity and was found to predominate; type II was spatially separated from the AChE-positive NMJ, occurred less frequently and contained both AChE activity and NOS I. These data suggest that type II NMJ are provided with additional regulatory mechanisms, such as free radical signaling by the NOS I-derived NO which may exert modulatory effects on the choline acetyltransferase/ACh/AChE pathway. Furthermore, type II may represent those NMJ where recently glutamate-gated NMDA-type Ca2+ channels have been described, which in analogy to those in the nervous system may serve also in skeletal muscle fibers as NOS I activators.

Acetylcholinesterase↗
PubMed1997

Nitric oxide synthase (NOS) I during postnatal development in rat and mouse skeletal muscle.

Previous studies on adult rat and mouse skeletal muscles have shown the spatial association of nitric oxide synthase (NOS) I to the dystrophin complex (DC) in the sarcolemma of type II fibers and, in combination with the NMDA receptor-1 (NMDAR-1), an accumulation of the enzyme at the neuromuscular junctions (NMJ) of this fiber type. Using immunohistochemistry, enzyme histochemistry and alpha-bungarotoxin labeling we report here temporal relationships of NOS I, members of the DC, other components of the cortical cytoskeleton in the junctional and non-junctional sarcolemma as well as of molecules involved in NMJ transmission of either type I or II myofibers especially in head and neck muscles during postnatal rat and mouse development. Fiber typing was performed by specific anti-myosin antibodies. Beginning with postnatal day (PD) 1 in both fiber types dystrophin, dystrophin-associated glycoproteins (DAG), beta-dystroglycan, alpha-sarcoglycan (adhalin) and spectrin were present in the junctional and extrajunctional sarcolemma, while utrophin, acetylcholinesterase, alpha-bungarotoxin labeled acetylcholine receptors were concentrated in the NMJ of both fiber types. NOS I activity and immunoreactivity were only found in the NMJ region of type II fibers, where NMDAR-1 appeared around PD 15. Primarily in the tongue there was no strict correlation between muscle fiber type and NOS I behaviour during early postnatal development, and muscle fibers not reactive for myosin antibodies against both fiber types were negative or positive for NOS I but always positive for the other molecules either in both the junctional and extrajunctional sarcolemma or in the NMJ only; later all muscle fibers of the tongue were of type II and NOS I-positive. Maturation of enzyme activities, immunoreactivities and AChR intensity depended on the respective muscle and can last until PD 50; in the tongue and neck muscles they appeared to increase approximately until PD 20 or 25. In conclusion, in type II fibers of rat and mouse skeletal muscle all molecules with the exception of NMDAR-1 and relevant for NOS I targeting and positioning as well as function inside and outside the NMJ are already present at birth, but their concentrations and/or activities increase postnatally, and the adult situation appears to be reached between the third and seventh week of postnatal life. Therefore, initial interactions between NOS I and the other molecules necessary for the formation of the NOS I-DC in and on the way to the sarcolemma presumably take place before birth.

Animals↗
PubMed1997

NO is not substantially involved in afferent signalling in rat muscle spindles.

As intrafusal nuclear bag and chain fibers of muscle spindles take part in both sensory and motor functions, these stretch receptors may represent a useful model to answer the question whether nitric oxide (NO) signalling is involved in sensory and motor functions or motor events only, as has already been shown for ordinary extrafusal fibers. To answer these questions, we have applied immunohistochemical and enzyme histochemical methods to serial transverse sections of the rat gastrosoleus muscle for determining the presence or absence of NOS I, NOS-associated diaphorase (NOSaD), AChE and proteins related to the dystrophin complex. NOS I, NOSaD, and AChE were practically absent from the equatorial (central) region of intrafusal fibers, i.e. the site of termination of the primary and secondary afferents. These regions showed weak staining for dystrophin, beta-dystroglycan as well as alpha- and gamma-sarcoglycan. By contrast, all of these molecules were found enriched in the polar (peripheral) regions of the intrafusal fiber sarcolemma. NOS I, NOSaD, dystrophin, beta-dystroglycan and the two sarcoglycans showed a general presence in the sarcolemma, whereas AChE was limited to the endplate region and other circumscribed areas. From these observations we would like to conclude that NO does not appear to be significantly or even not involved in signal transfer to the sensory nerve endings in the intrafusal fibers.

Acetylcholinesterase↗
PubMed1997

Absence of nitric oxide synthase I despite the presence of the dystrophin complex in human striated muscle.

Recently, it has been shown that in human striated muscle the signalling enzyme, brain-type nitric oxide synthase I (NOS I), is associated with the sarcolemma and complexes with dystrophin and/or members of the dystrophin complex. In order to find out whether there exists a regular association between NOS I and the complex, muscle biopsies from patients with various muscle disorders were analysed by enzyme histochemistry and immunohistochemistry. In patients suffering from Duchenne muscular dystrophy, and to a lesser extent in those with Becker-type dystrophy, NOS I and dystrophin complex components were absent or drastically reduced in the sarcolemma region. In other dystrophies, as well as in metabolic and inflammatory myopathies, NOS I and dystrophin complex constituents were expressed normally, while in the case of neurogenic diseases leading to denervation atrophy and especially congenital idiopathic clubfoot, the immunohistochemical patterns of the distribution of the dystrophin complex constituents were normal, but NOS I activity and protein were deficient or dramatically diminished. The results can be interpreted as indicating that, in general, NOS I targeting to the sarcolemma is dependent on particular members of the dystrophin complex, such as alpha-1 syntrophin, yet the expression and/or positioning of NOS I may be under the control of further factors, probably of neurogenic origin. NOS I-associated diaphorase may thus be a useful complementary tool in the diagnosis of muscle disorders.

Catalysis↗
PubMed1996

Colocalisation of NADPH-diaphorase with neuropeptides in the ureterovesical ganglia of humans.

Neurones in the ureterovesical ganglion complex provide autonomic innervation to the pelvic ureter, the ureterovesical junction and the bladder trigone. We examined the distribution and peptide co-expression pattern of nitric oxide synthase (NOS) in the human ureterovesical ganglia by combining NADPH-diaphorase histochemistry with immunoreactivity for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP). Less than 20% of nerve cells in the large ganglia of the ureterovesical complex were stained for NOS activity. In elderly individuals, ganglion cells regularly exhibited conspicuous morphological alterations suggestive of degenerative changes. Most of the NOS-positive cell bodies costained for VIP-immunoreactivity. A minority of NOS-expressing cells also reacted for NPY-immunoreactivity. CGRP-immunoreactivity was present in varicose terminal-like nerve fibres which were found to encircle NOS-containing perikarya. Occasionally, NOS-positive somata were surrounded by plexiform axon terminals which immunostained for VIP or NPY. We conclude that the passage of urine across the ureterovesical junction is under relaxatory control of a local nitric oxide/VIP(NPY) pathway which may be modulated by preganglionic efferent and/or primary afferent input.

Adult↗
PubMed1996

Adhalin (alpha-sarcoglycan) is not required for anchoring of nitric oxide synthase I (NOS I) to the sarcolemma in non-mammalian skeletal (striated) muscle fibers.

Previous studies have shown the association of NOS I with the sarcolemma in mammalian striated muscle fibers, implicating the dystrophin complex (DC) as a major anchor for the enzyme. The potential role of the sarcoglycan subcomplex, especially of alpha-sarcoglycan (adhalin), as part of the DC in holding of NOS I in the sarcolemmal position was examined by carrying out a comparative study on the distribution of NOS I, dystrophin, dystrophin-associated glycoproteins (DAG) and alpha-sarcoglycan in various skeletal muscles of non-mammals. Rat muscles were included since they reflect the situation in mammals. Catalytic NOS-associated diaphorase (NOSaD) activity as well as NOS I and DAG immunoreactivities were positive in the saracolemma region of skeletal muscle fibers of rats, chicken, and turtles. Adhalin immunoreactivity was present in the rat but absent in the chicken and turtle muscle surface membrane. These data suggest that alpha-sarcoglycan and therefore the entire sarcoglycan subcomplex may not be needed for localizing NOS I to the sarcolemma in these non-mammalian species. This may hold for skeletal muscle fibers in general.

Animals↗
PubMed1996

Nitric oxide synthase I immunoreactivity and NOS-associated NADPHd histochemistry in the visceral epithelial cells of the intraplacental mouse yolk sac.

In the course of our studies on the local blood flow modulation in the NMRI-mouse placenta we have focussed on regulatory pathways involving recently appreciated gaseous messenger molecules nitric oxide (NO) and carbon monoxide (CO), which are generated by NO synthase (NOS) and heme oxygenase (HO)-2, respectively. The distribution of NOS was investigated by immunohistochemistry using an antiserum to the neuronal isoform (NOS-I) and by NADPH diaphorase (NADPHd) histochemistry, supplemented with procedures (permanganate and formaldehyde method) serving to enhance the specificity of the enzyme histochemical method for NOS visualization. HO-2 was demonstrated immunohistochemically. In addition, cyclic guanosine monophosphate (cGMP)-forming soluble guanylate cyclase (sGC) and dehydrogenases generating the NOS co-substrate NADPH were analysed either by immunohistochemistry or enzyme histochemistry. NOS-I immunostaining was observed in the intraplacental visceral yolk sac epithelial cells but not in the placenta and extraplacental visceral epithelial yolk sac cells. Co-localization of NOS-I immunolabeling and NOS-associated NADPHd was exclusively found in the intraplacental visceral epithelial cells, while NADPHd activity not associated to NOS was present in other placental and extraplacental cells additionally analysed for control reasons. HO-2 and sGC immunoreactivity could not be detected in the placenta including the intraplacental visceral epithelial cells but were expressed in several extraplacental cells. Dehydrogenases producing the NOS co-substrate NADPH were present in the intraplacental visceral epithelium as well as in other placental and extraplacental cells. Since the intraplacental visceral epithelial yolk sac layer closely accompanies large fetal blood vessels entering the placental labyrinth from the chorionic plate it may be assumed that NO, generated by the NADPH-consuming NOS-I in the intraplacental yolk sac epithelium, acts to regulate the blood flow by relaxing smooth muscle cells in the wall of these fetal vessels. The lack of immunoreactivity to the NO-effector molecule sGC may be due to methodological reasons. The absence of the HO-2/CO system suggests its insignificant role as a potential gas signaling pathway in the vascular smooth muscle system of the intraplacental visceral yolk sac of mice.

Animals↗
PubMed1996

Expression of heme oxygenase-2 (HO-2)-like immunoreactivity in rat tissues.

Microsomal heme oxygenase (HO) is a cytochrome P-450-assisted oxidoreductase, which catalyzes the NADPH-dependent decomposition of heme to carbon monoxide (CO), biliverdin, and iron. Recent evidence suggests that CO, similar to nitric oxide (NO), may serve as gaseous biological signalling molecule, which acts by stimulating soluble guanylate cyclase in target cells. In the present investigation, we report the HO-like immunoreactivity (LIR) pattern of the constitutive HO isozyme, HO-2, and compare the results with recently published data on constitutive NO-producing nitric oxide synthase (NOS) in rat tissues. HO-2-LIR was most consistently observed in connective tissue elements (fibrocytes/-blasts and fibroblast-like cells, such as interstitial cells in the bowel), blood vessel wall constituents (arterial and venous endothelial cells, vascular smooth muscle cells), visceral smooth muscle cells (airway musculature, myometrium, muscularis mucosae of the small intestine), mesothelial cells of serous membranes and in select epithelial cell populations. HO-2-LIR was absent from the striated (skeletal and cardiac) musculature. HO-2 had a more widespread distribution and its expression largely differs from that of NOS. HO-2-LIR and NOS appear to be co-expressed in vascular endothelial cells and in selected nerve cell populations of certain parasympathetic and probably sensory ganglia. Our data suggest potential CO and NO systems as interrelated regulatory pathways in the local paracrine and autocrine control of diverse functional systems.

Animals↗
PubMed1996

Nitric oxide synthase I (NOS-I) is deficient in the sarcolemma of striated muscle fibers in patients with Duchenne muscular dystrophy, suggesting an association with dystrophin.

Previously, we have demonstrated the expression of the brain-type nitric oxide synthase (NOS-I) in the sarcolemmal region of somatic and visceral striated muscle fibers in a variety of mammalian species through the use of enzyme histochemical and immunochemical techniques. Here we report that NOS-I protein and its NADPH diaphorase (NADPHd) activity are co-localized in the sarcolemma of human skeletal muscles. NOS-I immunolabeling and NADPHd activity showed no significant variation between type I and II fibers. In muscle biopsy specimens from patients with Duchenne muscular dystrophy (DMD), both NOS-I protein and activity were absent or markedly reduced. We, therefore, propose that NOS-I is complexed with dystrophin and/or dystrophin-associated proteins, adding a novel member to the sarcolemmal dystrophin-glycoprotein complex (DGC). The nature of the NOS-I-DGC link, and its role in skeletal muscle physiology and pathophysiology remain to be elucidated.

Child↗
PubMed1995

Nitroxergic innervation of the human ureterovesical junction.

Nitric oxide synthase (NOS) immunohistochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were used to investigate the distribution of nitroxergic, i.e., nitric oxide-synthesizing, neuronal perikarya and processes in the human ureterovesical junction (UVJ). Tissue specimens obtained from two cadaver kidney donors and two patients undergoing radical cystectomy for bladder cancer were examined. Clusters of NOS-immunoreactive neurons were localized in extramural ureterovesical ganglia. NOS-containing nerve fibers traveled within large extramural nerve trunks and marched among smooth muscle bundles. Extramural and intramural blood vessels were encircled by varicose NOS-positive axonal processes. The distribution of NOS immunoreactivity paralleled the staining pattern for NADPH-d activity. Urothelium stained strongly for NADPH-d activity but showed no NOS immunolabeling. Specimens from all four patients investigated showed similar staining patterns. Our results suggest that nitric oxide, a potent smooth-muscle-relaxing neurotransmitter in the autonomic nervous system, plays a physiologic role in opening the human UVJ.

Adult↗
PubMed1995

Species-independent expression of nitric oxide synthase in the sarcolemma region of visceral and somatic striated muscle fibers.

The expression and distribution of nitric oxide synthase (NOS) was studied by use of the newly designed specific histochemical NADPH diaphorase staining method and the indirect immunofluorescence technique employing an antiserum to brain NOS in visceral and somatic striated muscles of several mammalian species. Histochemical activity and immunoreactivity were located in the sarcolemma region of type I and II fibers of all muscles investigated. Visceral muscles were more strongly stained than somatic muscles. Furthermore, type II fibers, identified by staining of myosin adenosine triphosphatase activity after pre-incubation at alkaline pH, were more intensely labeled than type I fibers. In addition, NOS activity was detected in the area of the sarcolemma of intrafusal fibers. No obvious differences between species were observed. It was concluded that NOS of striated muscles probably makes up the richest and most important nitric oxide source in mammals.

Animals↗