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)

Rat lumbar dorsal root ganglion neurones projecting to the nucleus gracilis in the brainstem were retrogradely labelled with Fluoro-Gold and analysed immunocytochemically for their expression of substance P-, calcitonin gene-related peptide-, galanin-, galanin message-associated peptide-, neuropeptide Y-, nitric oxide synthase- and carbonic anhydrase-like immunoreactivity as well as affinity to Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4, RT97 and to choleragenoid. The analysis was made both in uninjured rats and in rats which had been subjected to unilateral sciatic nerve transection and partial resection 3 weeks earlier. The data showed that 6% of the L4 and L5 lumbar dorsal root ganglion cells that projected to the nucleus gracilis showed substance P-like immunoreactivity. Following nerve injury, none of the nucleus gracilis-projecting dorsal root ganglion cells showed substance P-like immunoreactivity. Nineteen per cent of the investigated cell population showed calcitonin gene-related peptide-like immunoreactivity in uninjured rats, but no nucleus gracilis-projecting calcitonin gene-related peptide-positive cells were found after nerve injury. Galanin- and galanin message-associated peptide-like immunoreactivity were found in 2% and 3%, respectively, of the Fluoro-Gold-labelled cell population normally and in 22% and 14%, respectively, after injury. No neuropeptide Y-positive cells were found in the Fluoro-Gold-labelled cell population normally, but after nerve injury, 96% of this population became neuropeptide Y-positive. Nitric oxide synthase-like immunoreactivity was found in 2% of the Fluoro-Gold-labelled cells normally and in 10% after injury. Two per cent of the Fluoro-Gold-labelled cells in the normal cases were stained by Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4. After injury, however, no such double labelling was found. Thirty-four per cent of the Fluoro-Gold-labelled cell population was carbonic anhydrase positive normally, and 42% after injury. Seventy-five per cent of the Fluoro-Gold-labelled cells showed RT97 immunoreactivity normally and 12% after injury. Choleragenoid-like immunoreactivity was found in 99% of the Fluoro-Gold-labelled dorsal root ganglion cells normally and 81% after injury. Immunohistochemical visualisation of choleragenoid transganglionically transported from the injured sciatic nerve combined with neuropeptide Y immunocytochemistry showed that primary afferent fibres and terminals in the nucleus gracilis contain neuropeptide Y following peripheral nerve transection. Taken together, the results indicate that peripherally axotomised nucleus gracilis-projecting neurones undergo marked alterations in their cytochemical characteristics, which may be significant for the structural and functional plasticity of this system after injury.
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PMID:The expression of different cytochemical markers in normal and axotomised dorsal root ganglion cells projecting to the nucleus gracilis in the adult rat. 749 88

The present study was undertaken to investigate the in vivo effects of nitric oxide (NO) mediating agents injected intracavernosally on penile erection in cats. All NO donors increased the cavernosal pressure and penile length in a dose-dependent manner. The maximal effects on cavernosal pressure and penile length induced by s-nitrosocysteine (NO-CYS) and s-nitroso-n-acetylpenicillamine (SNAP), respectively, were 8-fold and 5-fold increases in pressure, and 45% and 34% increases in length when compared with baseline values. These changes were comparable to that caused by the control drug combination (papaverine, phentolamine and prostaglandin E1). The effects of acetylcholine (ACh) and substance P on cavernosal pressure and penile length were less than those obtained with the control drug combination, NO-CYS (p < 0.01), or SNAP (p < 0.05). N omega-nitro-l-arginine-methyl-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly decreased the effects of NO-CYS, ACh and substance P on penile erection. This in vivo study with NO donors and an NOS inhibitor suggests that NO is a mediator of penile erection in cats.
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PMID:Nitric oxide mediates penile erection in cats. 750 45

The carotid body is an arterial chemoreceptor organ sensitive to blood levels of O2, CO2 and pH. The present immunocytochemical and neurochemical study has demonstrated the presence of an extensive plexus of nitric oxide (NO)-synthesizing nerve fibers in this organ. These nitric oxide synthase (NOS)-containing axons are closely associated with parenchymal type I cells and with blood vessels in the carotid body. Denervation and retrograde tracing experiments have revealed that these fibers arise from NOS-immunoreactive and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neuronal cell bodies located in the petrosal ganglion and the carotid body, and dispersed along the glossopharyngeal and carotid sinus nerves (CSN). Within the petrosal ganglion, these neurons are topographically segregated from the catecholaminergic cells, and they contain the neuropeptide, substance P. NOS-positive autonomic microganglial cells in the carotid body and CSN also exhibit choline acetyltransferase (ChAT) immunoreactivity. Our results suggest that nitric oxide may be a novel neuronal messenger in the mammalian carotid body involved in the modulation of chemosensory transduction and transmission in this organ.
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PMID:Neurons synthesizing nitric oxide innervate the mammalian carotid body. 750 96

In the basal ganglia, centrally active suicide transport agents produce apparently selective lesions of the striatopallidal and striatonigral pathways based on receptor binding and neuropeptide mRNA studies. In the present study we sought to determine the selectivity of suicide transport lesions for specific subsets of striatal neurons. Using immunohistochemical methods, the neostriata of adult rats were examined 10 days after an injection of volkensin into the substantia nigra or an injection of OX7-saporin into the globus pallidus. Ricin, a suicide transport agent active in the peripheral but not the central nervous system, was injected into each target as a control. Adjacent sections were processed for (1) Nissl stain to assess neuronal density, both overall and for large interneurons, (2) NADPH-diaphorase (NADPH-d) histochemistry, to mark medium-sized aspiny interneurons, (3) enkephalin immunocytochemistry, to label striatopallidal neurons, or (4) substance P immunocytochemistry, to label striatonigral neurons. Ricin injections produced no change in the densities of these subsets of striatal cells. In animals receiving volkensin or OX7-saporin injections, analyses of Nissl material revealed that the striata ipsilateral to the toxin injections appeared normal and did not exhibit shrinkage or gliosis; however, a quantitation analysis revealed a moderate decrease in cell density (12-16% loss, P < 0.01). The densities of both large and NADPH-d-containing striatal interneurons were unchanged after lesions in either target. Following nigral injections with volkensin, the density of striatal substance P-labeled cells decreased (26% loss, P < 0.01), while the density of enkephalin-labeled cells did not decrease significantly (11% decrease, P > 0.1). After pallidal injections with OX7-saporin, the density of striatal enkephalin-labeled cells decreased (20% loss, P < 0.01), while that of substance P-labeled cells remained unchanged. These data show that nigral volkensin and pallidal OX7-saporin injections differentially lesion striatonigral and striatopallidal projection neurons and spare striatal interneurons. This study provides further evidence for the selectivity, specificity, and utility of suicide transport agents to study brain structure and function.
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PMID:Differential effects of suicide transport lesions of the striatonigral or striatopallidal pathways on subsets of striatal neurons. 750 60

Within the human adrenal medulla immunoreactivity for the nitric oxide (NO)-generating enzyme nitric oxide synthase (NOS) was demonstrated in neurons, nerve fibres and chromaffin cells. Correlation of NOS-immunoreactivity with immunostaining for the peptides neuropeptide Y, somatostatin, substance P or vasoactive intestinal polypetide and for the catecholamine synthesis-enzyme tyrosine hydroxylase, respectively, in nerve cell bodies revealed colocalization of NOS only with substance P. Sparse intramedullary NOS-immunoreactive varicose nerve fibres associated with blood vessels or with chromaffin tissue were devoid of immunoreactivities for tyrosine hydroxylase or for the investigated peptides. Small NOS-immunolabeled cells belonged to the catecholamine-containing chromaffin cell population and costored VIP, but were distinct from the somatostatin- or neuropeptide Y- immunostained chromaffin subpopulations. The localization of NOS in distinct structural components of the human adrenal medulla indicates that NO is produced in different cell types and may reflect a differential role of this messenger system in autonomic control of adrenal gland function.
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PMID:Immunohistochemical demonstration of the synthesis enzyme for nitric oxide and of comediators in neurons and chromaffin cells of the human adrenal medulla. 750 10

The ultrastructural distribution and subcellular localization of nitric oxide synthase (NOS) immunoreactivity and its possible colocalization with vasoactive intestinal polypeptide (VIP) and substance P in the muscularis externa in canine ileum and colon were studied by using polyclonal antisera raised against VIP, substance P, and cerebellar NOS. Immunogold staining, with or without silver enhancement, was carried out directly on ultrathin sections using single and two-faced double immunogold methods. NOS immunoreactivity was observed in nerve profiles in myenteric plexus and circular muscle layer. Immunoreactivity was occasionally detected in smooth muscle cells and interstitial cells of Cajal. The double immunostaining revealed NOS and VIP in the same nerve varicosities but never in the same organelles. NOS was localized in electron-dense material of undetermined nature, whereas VIP was associated with large granular vesicles. Substance P and NOS were never found in the same nerves. These results indicate that NOS is present in the enteric nerves containing VIP but in different organelles and that nitric oxide release probably does not occur by an exocytotic mechanism.
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PMID:Ultrastructural localization of nitric oxide synthase in canine small intestine and colon. 751 56

Recent studies suggest that muscle stretch and mucosal stimulation elicit intestinal peristalsis by activating distinct populations of sensory neurons that converge on the same population of enteric motor neurons. The present study sought to characterize the origin and projections of these sensory neurons. The reflex was elicited by applying muscle stretch and mucosal stroking to the central compartment of a three-compartment flat-sheet preparation of rat colon while ascending contraction and descending relaxation were measured in the orad and caudad compartments, respectively. Identical graded responses were elicited by muscle stretch and mucosal stimulation: atropine (1 microM) and the tachykinin antagonist spantide (10 microM) inhibited ascending contraction when added to the orad compartment only, while the vasoactive intestinal peptide antagonist VIP10-28 (10 microM) and the NO synthase inhibitor NG-nitro-L-arginine (100 microM) inhibited descending relaxation when added to the caudad compartment only. Addition of capsaicin (1 microM) to the central compartment for 30 min abolished ascending contraction and descending relaxation elicited by muscle stretch and mucosal stimulation. Recovery of response was complete when capsaicin was applied to the mucosa of the colon in situ and measurements made 1 d after, implying that at this low concentration capsaicin depleted sensory nerve terminals of their transmitter content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinct populations of sensory neurons mediate the peristaltic reflex elicited by muscle stretch and mucosal stimulation. 751 13

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.
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PMID:Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P. 751 84

Expression of nitric oxide synthase (NOS) was investigated in neurons of lumbar spinal cord of adult rats following subcutaneous injection of formalin (FOR) in one hindpaw. NOS was visualized immunocytochemically using a specific antibody and by the NADPH-diaphorase reaction (NDP). In the untreated rat, NOS immunoreactivity (IR) and NDP were present in neurons of the superficial dorsal horn (sDH) predominantly in layers II-III, and in the deep dorsal horn (dDH) predominantly in layer X. Twenty-four hours following FOR, the numbers of neurons labelled for NOS and NDP and the density of NDP containing nerve fiber varicosities significantly increased in sDH of the ipsilateral L3-L4 segments. NOS-IR and NDP gave a rather congruent distribution of labelled neurons in the dorsal horn. In contrast, distinct NOS-IR but not NDP was visible in large diameter motoneurons and in the lateral spinal nucleus. Double labelling demonstrated that in sDH most of the NDP-reactive neurons show a close spatial relationship to fibers and varicosities immunoreactive for substance P and CGRP. These neuropeptides are considered mediators of synaptic input from nociceptive primary afferents. Colocalization of NDP with c-Jun, JunB, JunD, c-Fos, FosB and Krox-24 transcription factors was investigated in neurons of lumbar spinal cord. c-Jun, JunB, c-Fos and Krox-24 reached their maximal levels of expression 2 h after FOR and returned to basal levels after 10 h. FosB and JunD reached their maximal expression after 5 h, persisted up to 10 h and were still visible in 60%-70% of the maximal number of labelled nuclei after 24 h. This persistent expression of transcription factors might contribute to the up-regulation of NOS expression between 10 h and 24 h. In a low number of NDP neurons, suprabasal immunoreactivity of JunB, c-Fos and Krox-24 proteins was visible up to 10 h, and of JunD and FosB up to 24 h in sDH neurons; c-Jun was not expressed in NDP labelled neurons of sDH, but, similar as JunD, showed basal colocalization in preganglionic sympathetic and parasympathetic neurons. In dDH, colocalization of Jun, Fos and Krox-24 proteins in few neurons was only observed following a second FOR stimulus given 24 h after the first one. Double-staining also demonstrated that many Jun, Fos and Krox labelled neurons are in close proximity to NDP labelled nerve fibers suggesting a functional relationship between expression of immediate-early gene encoded transcription factors and presence of nitric oxide in the rat spinal cord.
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PMID:Expression of nitric oxide synthase and colocalisation with Jun, Fos and Krox transcription factors in spinal cord neurons following noxious stimulation of the rat hindpaw. 751 94

The comparative effects of the nitric oxide (NO) synthase inhibitors N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME), and N omega-nitro-L-arginine benzyl ester (L-NABE) on baseline tone and on vasodilator responses to acetylcholine (ACh), bradykinin (BK), and substance P (SP) were compared in the pulmonary vascular bed of the cat under constant flow conditions. After administration of the NO synthase inhibitors in intravenous doses of 100 mg/kg, the increase in lobar arterial pressure and the attenuation of vasodilator responses to ACh, BK, and SP were similar, whereas responses to adenosine and felodipine, endothelium-independent vasodilator agents, were not altered. In addition to inhibiting responses to ACh, BK, and substance P, the NO synthase inhibitors enhanced vasodilator responses to S-nitroso-N-acetylpenicillamine and NO. Moreover, atropine inhibited pulmonary vasodilator responses to ACh but not to SP or BK, and L-NAME or L-NABE had no effect on the decrease in heart rate in response to efferent vagal stimulation, a muscarinic receptor-mediated response that is independent of NO release. The similar inhibitory effects of L-NNA, L-NAME, and L-NABE on vasodilator responses to ACh, BK, and SP suggest that the L-arginine analogue, L-NNA, as well as the methyl and benzyl esters of L-NNA are useful probes for studying NO-mediated endothelium-dependent responses in the pulmonary vascular bed of the intact-chest cat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of L-NNA and alkyl esters of L-NNA on pulmonary vasodilator responses to ACh, BK, and SP. 751 47


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