Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuroendocrine nature of a subset of Leydig cells has already been established. The present investigation deals with neuroendocrine characteristics of Leydig tumour cells. A number of neuroendocrine and neuronal markers were demonstrated in Leydig cell tumours of 7 men aged 25-41 years. The following substances were immunocytochemically tested in Leydig tumour cells: the monoamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, the indoleamine serotonin, the calcium-binding protein parvalbumin, the microtubule associated protein-2, neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and neuronal nitric oxide synthase (NOS). Compared to the normal interstitial cells beyond the tumours, all neoplastic cells showed a significantly weaker immunoreactivity for nerve cell markers as well as for testosterone and cyclic guanosine monophosphate (cGMP), which is usually accumulated by nitric oxide (NO). This provides evidence for a certain dedifferentiation of Leydig tumour cells. However, these results suggest that tumourous development of Leydig cells does not include loss of neuronal phenotype. Moreover, on the assumption that 'neuronal' Leydig cells exist beside 'non-neuronal' ones in normal testicular tissue, we propose the hypothesis that 'neuronal' Leydig cells can transform to tumour cells.
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PMID:Neuroendocrine characteristics of human Leydig cell tumours. 859 7

The mediator accounting for the major relaxant responses to electrical field stimulation of human airways was previously identified as nitric oxide (NO). In the present study, we examined the distribution of the neuronal isoform of the NO-generating enzyme, nitric oxide synthase (bNOS, type I NOS) in nerve fibers of the human airways (trachea, large and small bronchi, bronchioli) as well as in human intrinsic and sensory ganglia of airway innervation by means of quantitative histochemistry (NADPH-diaphorase technique) and immunohistochemistry. Correlation with substance P (SP) and vasoactive intestinal peptide (VIP) was performed by double-labeling immunohistochemistry. NOS-containing nerve fibers were found to be present in the airway smooth muscle, around submucosal glands, around blood vessels and, very rarely, in the lamina propria. The innervation density of airway smooth muscle by NOS-containing nerve fibers decreased significantly from trachea to large-diameter bronchi to small-diameter bronchi, whereas NOS-containing nerve fibers were completely absent from bronchioli. Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers. In airway intrinsic ganglia, the number of NOS-containing neuronal cell bodies increased from 57% in the trachea up to 83% in small bronchi. Around these perikarya, many nerve fibers displaying VIP-immunoreactive (VIP-IR) or SP-IR were found. In the superior vagal sensory (i.e., jugular) ganglion most of the neuronal cell bodies contained either NOS-IR or SP-IR; a colocalization of both was not as frequent. These data contribute to the understanding of the morphologic basis underlying the functional differences of the neural relaxant responses mediated by NO at different levels of the airway tree.
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PMID:Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides. 868 Jun 82

To establish which type of nerves (parasympathetic, sympathetic or sensory) produce nitric oxide in the rat lower urinary tract, chemical denervation of primary afferents and sympathetic nerves was carried out by systemic treatment with capsaicin and 6-hydroxydopamine, respectively, followed by identification of neuronal nitric oxide synthase immunoreactivity. Functional in vitro studies were also performed to examine whether the synthesis and release of nitric oxide was affected following treatment with the respective neurotoxins. Nerve fibres immunoreactive for substance P and calcitonin gene-related peptide were found in control tissue, but could not be detected following capsaicin treatment. In comparison, nitric oxide synthase-immunoreactive fibres appeared to be unaffected by capsaicin treatment. Administration of 6-hydroxydopamine resulted in a complete disappearance of tyrosine hydroxylase-immunoreactive nerves, whereas nitric oxide synthase-containing nerve fibres did not appear to be affected by the treatment. In ultrastructural studies, nitric oxide synthase immunoreactivity, as studied by colloidal gold particles, was found in the axoplasm and not in association with intraneuronal structures or synaptic vesicles. Gold particles representing substance P immunoreactivity were seen as clusters associated with large granular vesicles. In consecutive sections of nerve fibres, substance P and nitric oxide synthase were not found in the same axon profile. In functional studies on urethral tissue, application of capsaicin (1 microM) produced a long-lasting relaxation. The nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) had no effect on this response. Systemic treatment with capsaicin or 6-hydroxydopamine had no effect on nerve-evoked, nitric oxide-mediated relaxations. The data suggest that nitric oxide synthase-containing nerves in the rat lower urinary tract do not belong to nerve populations sensitive to either the sympathetic neurotoxin, 6-hydroxydopamine, or the sensory neurotoxin, capsaicin.
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PMID:Morphological and functional evidence against a sensory and sympathetic origin of nitric oxide synthase-containing nerves in the rat lower urinary tract. 904 92

L-Tyrosyl-L-arginine (kyotorphin) is known as an endogenous analgesic neuropeptide. We examined whether kyotorphin and other arginine-containing neuropeptides were endogenous substrates for neuronal nitric oxide synthase (NOS) in the rat brain. Cytosol fractions of the rat cerebellum contained higher concentrations of neuronal NOS (nNOS) than endothelial NOS. In rat cerebellar cytosol, the binding activity of [3H]NG-nitro-L-arginine (NNA) was inhibited equally by L-arginine (L-Arg), kyotorphin, and L-leucyl-L-Arg (a kyotorphin receptor antagonist). Binding activities were inhibited to lesser degrees by fibronectin active fragments, bradykinin, and dynorphin A, but were not inhibited by L-tyrosyl-D-Arg or substance P. Interestingly, the inhibition of [3H]NNA binding by kyotorphin was attenuated by inhibitors of kyotorphin-hydrolyzing peptidases (KTPases) such as bestatin and arphamenine B. These results suggest that kyotorphin is degraded to L-Arg by KTPases, which in turn may act as substrate for nNOS.
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PMID:Effects of kyotorphin (L-tyrosyl-L-arginine) ON[3H]NG-nitro-L-arginine binding to neuronal nitric oxide synthase in rat brain. 915 2

Previous studies have shown that the guinea pig inferior mesenteric artery receives spinal sensory vasodilatory innervation, which can be activated by colon distention and electrical nerve stimulation. In the present study, we investigated the hypotheses that nitric oxide synthase (NOS) is present in guinea pig primary sensory neurons in the dorsal root ganglion (DRG) and in nerve fibers surrounding the mesenteric arteries, and that nitric oxide (NO) is a sensory neurotransmitter in the inferior mesenteric artery in vitro. Double-labeling immunohistochemistry showed that neuronal NOS-IR was found in 12% of cells of guinea pig thoracic and lumbar DRGs; in 95.1% of these cells it was colocalized with substance P (SP), and SP immunoreactivity (SP-IR) was present in 23% of cells of the same DRGs. Neuronal NOS-like immunoreactivity was localized in nerve fibers surrounding guinea pig mesenteric artery and 25% of them were double stained with SP-IR. Endothelium-denuded inferior mesenteric artery preparations in vitro were incubated with guanethidine (30 microns, 30 min) and pre-contracted with methoxamine (30 microns). The NO donors, sodium nitroprusside (1 micron) and L-nitrosocysteine (300 microns), produced 91.0 +/- 5.5 and 90.4 +/- 9.6% vasodilatation of total vasodilatation in the vessel segments, respectively, which was capsaicin- or tetrodotoxin-insensitive. Repetitive electrical field stimulation of the preparations produced a frequency-dependent vasodilatation which was reduced by pretreatment with capsaicin or by tetrodotoxin (10 microns). The NOS inhibitor N omega-nitro-L-arginine (L-NNA) (100 microns, 30 min) diminished the nerve-evoked vasodilatation from 41.8 +/- 8.4 to 21.4 +/- 9.7% at 2 Hz and from 50.8 +/- 5.6 to 19.0 +/- 7.3% at 15 Hz (P < 0.05), whereas NG-nitro-L-arginine methyl ester (L-NAME, 100 microns-1 mM) did not significantly inhibit the relaxation. The stereo isomer nitro-D-arginine (D-NNA, 100 microns, 30 min) was ineffective. These findings suggest that NO is a neurotransmitter released from primary sensory nerves which mediates vasodilation in vitro.
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PMID:Nitric oxide is a sensory nerve neurotransmitter in the mesenteric artery of guinea pig. 947 65

The effects of a neuronal nitric oxide synthase (nNOS) inhibitor, 1-(2-trifluoromethylphenyl)imidazole (TRIM) on rat sensory saphenous nerve-induced neurogenic inflammation were investigated. TRIM (50 mg kg-1, i.p.), but not 2-trifluoromethylphenol (TRIMPOH) which lacks nNOS inhibitory activity, inhibited neurogenic oedema by 55.8 +/- 6.5% (n = 6, p < 0.05). The effect of TRIM was partially reversed by L-arginine (100 mg kg-1, i.v., p < 0.01). TRIM also caused a reduction (p < 0.05) in neurogenic vasodilatation but had no effect on neuropeptide responses induced by substance P + CGRP. Topically applied TRIM (100 microliters of 150-250 mg ml-1) inhibited neurogenic oedema (p < 0.01). Thus, use of this recently described nNOS inhibitor has provided new evidence to further the hypothesis that nNOS plays a role in modulating sensory nerve-mediated neurogenic inflammation.
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PMID:Neurogenic oedema and vasodilatation: effect of a selective neuronal NO inhibitor. 963 58

Since nitric oxide has been found to control the function of many organs of the body by the non-adrenergic, non-cholinergic branch of the autonomic nervous system, we hypothesized that it might play a role in salivary secretion. Therefore, we investigated the distribution of nitric oxide synthase (NOS) throughout the submaxillary gland and also studied the ability of inhibitors of NOS to interfere with salivation induced by a cholinergic agonist, metacholine, and by a polypeptide, substance P. The secretory responses were determined in rats anesthetized with chlorolose following intravenous injection of the various pharmacological agents. There was no basal flow of saliva and dose-response curves were obtained by sequential intravenous injection of increasing doses of the drugs. Then, in the same animal, the same dose-response curves were performed in the presence of NOS inhibitors. L-Nitro-arginine-methyl-ester (L-NAME; 20 mg/kg) produced an over 50% inhibition of the dose-related salivation induced by metacholine. Similar results were produced with L-NG-monomethyl-L-arginine (L-NMMA; 5 mg/kg). The salivation induced by much lower molar doses of substance P was dramatically greater than that obtained with metacholine. The response to substance P was almost completely inhibited by L-NMMA at the lowest dose (0.3 mg/kg), but at higher doses (1 mg/kg), the inhibition was only around 60% and at the highest dose (3 mg/kg) only about 20%. In control rats, there were roughly equal amounts of calcium-dependent and calcium-independent NOS in the gland at this time. At the end of the experiment, the effect of the inhibitor of NOS, L-NMMA, on the NOS activity in the submandibular gland was determined. At this time, the Ca2+-dependent NOS was decreased and the Ca2+-independent NO was increased. The prior injection of L-NMMA reduced calcium-dependent NOS activity by approximately 70% but calcium-independent activity by only 30%. These results indicate that, at least at the end of the experiment, the blockade of NOS imposed by NMMA was incomplete. This could account in part for the failure of the inhibitors to block completely the stimulatory effect of the two secretagogues. Analysis of the distribution of NOS in the salivary gland revealed that it was not present in the acinar cells, but in neural terminals within the gland and also in the ductile system which contained neural (n) NOS in the apical membrane of the excretory and striated ducts, the cytoplasm of granular convoluted tubules and, to a lesser extent, in the cytoplasm of excretory and striated ducts. Macrophage (inducible) NOS was also found not only in the macrophages, but also in the tubules and ducts. Since drugs were used that would act on the receptors in the gland, the role of NO in our conditions is probably mediated by nNOS and iNOS in the ductile and tubular structures. Since iNOS would already be active, it is unlikely to play a role in this acute secretory activity. Rather the nNOS in these non-neural cells is probably activated by muscarinic or K1 receptors by metacholine and substance P, respectively, leading to an increase in intracellular free calcium that activates NOS leading to the generation of cGMP that opens ion channels to initiate the secretory process.
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PMID:Role of nitric oxide in salivary secretion. 973 Jun 90

We have made an immunohistochemical study of the vomeronasal (VN) complex of 12-day-old rats to characterize the innervation of its blood vessels. The VN complex can be subdivided into rostral, middle and caudal segments, each one with a particular vascularization pattern. Several small vessels were associated with the rostral segment, whereas a large venous sinus ran along the middle and caudal segments. Immunostaining for alpha-smooth muscle actin demonstrated that the muscular sheath was asymmetric, with more cells layers in its lateral than in its medial walls. Nerves were demonstrated with antisera against protein gene product 9.5 (PGP), and against several molecules associated with specific classes of nerve fibers: the C-terminal peptide of neuropeptide Y (CPON), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (NOS). The latter, was also studied with NADPH-diaphorase. Vascular associated fibers exhibited NOS-, CPON-, GAL-, CGRP-, SP- and VIP-immunoreactivity. Only the vessels of the rostral segment showed VIP-immunoreactive fibers. Each wall of the venous sinus exhibited different types of nerve fibers. CPON-, GAL-, CGRP- and SP-immunoreactive fibers concentrated in the medial wall, whereas NOS-immunoreactive ones concentrated in the lateral wall. This distribution of vascular fibers, plus the presence of sensory fibers exhibiting CGRP-, SP- and GAL-immunoreactivity within the pseudostratified epithelium of the VN tube, would be relevant to understand the operation of the pumping mechanism regulating influx and efflux from the VN tube.
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PMID:Innervation of blood vessels in the vomeronasal complex of the rat. 980 88

The purpose of this study was to determine whether there is a specific organization of the primary sensory innervation on to identified vascular neurons in the inferior mesenteric ganglion (IMG) in guinea-pig. Retrograde tracers were placed intraluminally in inferior mesenteric artery (IMA) or inferior mesenteric vein (IMV) in vitro to identify ganglionic neurons as arterial, venous or unlabeled neurons. The distribution of primary sensory nerve fibers containing calcitonin gene-related peptide (CGRP), neuronal nitric oxide synthase (NOS) and substance P immunoreactivity (SP-IR) was compared before and after treatment with capsaicin. In control animals the density of immunoreactivity varied both with the transmitter and the type of neuron innervated. The density of immunoreactivity for all the three substances was reduced by capsaicin treatment. The degree of reduction of immunoreactivity in the fibers varied with the transmitter and the type of neuron. The density of CGRP and SP immunoreactive fibers was greatest around unlabeled neurons; 78% of the CGRP fibers were of primary sensory origin and all of the SP fibers were primary sensory. Around arterial neurons 44% of the CGRP fibers were of primary sensory origin and around venous 68% were primary sensory. NOS positive innervation around venous neurons was denser than around arterial neurons and all of it was completely (97%) eliminated by capsaicin, indicating that it was solely of primary sensory origin. We conclude that the primary sensory fibers innervating the IMG are differentially distributed to arterial and venous neurons and that the pattern of distribution is characteristic for each sensory neurotransmitter.
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PMID:Patterns of innervation of sympathetic vascular neurons by peptide-containing primary sensory fibers. 1032 Jun 99

In order to gain a better understanding of the neuronal and local control of inner ear blood flow, the vascular innervation to the rat cochlea and vestibular system was examined. Specimens were removed in toto beginning at the basilar artery extending to the anterior inferior cerebellar artery, labyrinthine artery, common cochlear artery, modiolar artery and anterior vestibular artery. When possible the vessels were dissected in continuity through the cribrose area. The vestibular endorgans were also removed. Specimens were examined using immunohistochemical techniques for the presence of vasoactive intestinal peptide, neuronal nitric oxide synthase, neuropeptide-Y, substance P and calcitonin gene related peptide. Results show that the vasculature to the cochlea and vestibular portion of the inner ear receive similar types of nonadrenergic innervation, that within the vestibular endorgans, only CGRP and SP were found in the neuroepithelium or in association with vessels, and that within the vestibular system, the majority of the vascular innervation appears to stop at or near the cribrose area. In the cochlea however, it extends to include the radiating arterioles. These findings suggest that cochlear blood flow is under finer control and that neuronally induced changes in blood flow may have a more global effect in the vestibular periphery.
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PMID:Comparison of the vascular innervation of the rat cochlea and vestibular system. 1071 7


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