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)

During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors.
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PMID:Selective muscarinic alterations of nitric oxide-mediated relaxations by neointima. 128 71

By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. NG-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, NG-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells.
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PMID:Endothelium-derived relaxing factor inhibits platelet adhesion to cultured porcine endocardial endothelium. 128 74

Intracellular microelectrodes were used to record junction potentials from the circular muscle cells of the guinea pig ileum in vitro at 37 degrees C in a modified Krebs solution containing nifedipine (1-2 microM) and hyoscine (1 microM). Transmural nerve stimulation, using volleys of three pulses at 50 Hz, produced a complex response consisting of an inhibitory junction potential (IJP) followed by a prolonged depolarization. Following the addition of the nitric oxide synthase inhibitor NG-nitro-L-arginine (NOLA, 100 microM) the amplitude of the IJP (recorded 10 mm aboral to the stimulating electrodes) was increased by approx. 10% (n = 4). The further addition of apamin (250 nM) abolished the IJP revealing a non-cholinergic excitatory junction potential (EJP). In other experiments (n = 8), preparations were treated with apamin then subjected to substance P desensitization (500 nM, > 20 min). Transmural nerve stimulation now produced a triphasic response (recorded 1 mm aboral to the stimulating electrodes) consisting of: (a) an initial hyperpolarization (approx. 5 mV) lasting about 1 s; followed by (b) a depolarization reaching a peak (approx. 7 mV less negative than the RMP) approx. 2 s after nerve stimulation; and finally (c) a small (approx. 3 mV) hyperpolarization. The addition of NOLA reduced all three phases by 80-90% (n = 8). The subsequent addition of L-arginine (5 mM) partially reversed these effects (n = 3). Conditioning hyperpolarization up to 20 mV increased the amplitude of the NOLA-sensitive IJP and EJP. Further conditioning hyperpolarization reduced the amplitude of the IJP and enhanced the amplitude of the EJP. Large conditioning hyperpolarizations (> 60 mV) reduced the amplitude of both the IJP and EJP. An estimation of the membrane conductance changes occurring during the initial hyperpolarization and depolarization suggest that it was either unchanged or increased. During large conditioning hyperpolarizations in the absence of nerve stimulation, the membrane potential was unstable and began to show spontaneous oscillations (up to 30 mV, every 4-5 s) resembling slow waves. These experiments indicate that NO, or a related compound, appears to mediate the nerve induced apamin-resistant IJP and substance P- and hyoscine-resistant EJP in the circular muscle of the guinea pig ileum.
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PMID:Effects of a nitric oxide synthase inhibitor on non-cholinergic junction potentials in the circular muscle of the guinea pig ileum. 128 61

The distribution of nitric oxide synthase (NOS) immunoreactivity was investigated in the guinea-pig small intestine. There were many immunoreactive nerve cell bodies in the myenteric plexus but very few in submucous ganglia. NOS immunoreactivity was not found in non-neuronal cells except for rare mucosal endocrine cells. Abundant immunoreactive nerve fibres in both myenteric and submucous ganglia, and in the circular muscle, arose from myenteric nerve cells whose axons projected anally along the intestine. NOS immunoreactivity coexisted with VIP-immunoreactivity, but not with substance P immunoreactivity. We conclude that nitric oxide synthase is located in a sub-population of enteric neurons, amongst which are inhibitory motor neurons that supply the circular muscle layer.
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PMID:Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. 128 39

The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.
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PMID:The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart. 129 66

The ventral lateral geniculate nucleus (vLGN) of the thirteen-lined ground squirrel (Citellus tridecemlineatus) is a highly differentiated nucleus that is divisible into five major subdivisions on the basis of retinal projections and cytoarchitecture. To pursue the likelihood that these subdivisions (the dorsal cap, intergeniculate leaflet, external magnocellular lamina, internal magnocellular lamina, and parvicellular segment) correlate with the functional diversity of this complex, the present study examined the neurochemical composition of the vLGN with regard to substances that have previously proved useful in distinguishing functionally distinct subregions within nuclei (i.e., neuropeptide Y (NPY), substance P (SP), leucine and methionine enkephalins, gamma-aminobutyric acid (GABA), cytochrome oxidase (CO), acetylcholinesterase (AChE), and NADPH-diaphorase). The results showed a clear differential neurochemical distribution within the nucleus. Neuropeptide Y immunoreactive perikarya were found predominantly in the intergeniculate leaflet and external magnocellular lamina, with only a few present in the internal magnocellular lamina and dorsal cap, and none observed in the parvicellular segment. NPY+ fibers, however, were present in all divisions except the parvicellular segment. The highest concentration of SP immunoreactive cells was observed in the internal magnocellular lamina, and substantial numbers also were scattered in the external magnocellular lamina and parvicellular segment. SP+ fibers were seen predominantly in the intergeniculate leaflet and the magnocellular laminae. The heaviest concentration of enkephalinergic fibers occurred in the internal magnocellular lamina and dorsal cap, but fibers were also observed in the external magnocellular lamina and intergeniculate leaflet. GABA reactivity was widespread throughout the vLGN, with the dorsal cap and external magnocellular lamina most heavily labeled, followed by the intergeniculate leaflet and the internal magnocellular lamina. Cytochrome oxidase, AChE, and NADPH-diaphorase histochemistry revealed rich reactivity within the dorsal cap, and external and internal magnocellular laminae and paler reactivity in the intergeniculate leaflet and parvicellular segment. The external magnocellular lamina was more reactive for CO and NADPH-diaphorase than AChE, while the internal magnocellular lamina showed the opposite pattern of reactivity. In addition, NADPH-diaphorase reactive cells were present in caudal intergeniculate leaflet and lateral external magnocellular lamina. These local differences in the neurochemical character of the vLGN support its parcellation into multiple subdivisions. Taken in conjunction with the differences in cytoarchitecture and retinal projections, these results suggest substantial functional diversity within the ventral lateral geniculate complex.
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PMID:Immunohistochemical organization of the ventral lateral geniculate nucleus in the ground squirrel. 137 67

We investigated the possibility of nitric oxide (NO), a powerful vasodilator agent, being synthesized by perivascular nerve fibres. Immunoreactivity and catalytic activity of the NO synthesizing enzyme, NO synthase (NOS), were demonstrated in perivascular nerve fibres of blood vessels receiving autonomic vasodilator innervation, but not of those innervated exclusively by vasoconstrictor nerve fibres. Double-labelling techniques allowed identification of NOS-containing nerve fibres as belonging to the vasoactive intestinal peptide (VIP)/acetylcholine-containing class whereas noradrenergic and substance P-containing perivascular fibres were devoid of NOS. We suggest that, in addition to its endothelial source, NO is a neuronal co-mediator of VIP/cholinergic vasodilation.
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PMID:Nitric oxide synthase in VIP-containing vasodilator nerve fibres in the guinea-pig. 138 69

1. The effect of an acetly-coA lysolecithin acyltransferase inhibitor, thimerosal, on the release of endothelium-derived relaxing factor (EDRF) was examined in the greyhound isolated coronary artery. 2. Thimerosal (1-10 microM) relaxed fully, ring segments of coronary artery which were contracted with the thromboxane A2-mimetic, U46619 (30 nM). The response was endothelium-dependent, slow in both onset and time to reach maximum. The maximum relaxation to the highest concentration of thimerosal (10 microM) was maintained for 10-20 min before the tissue slowly regained active force (1-2 h) to the same or higher level as that prior to the addition of thimerosal. At this time the endothelium-dependent relaxation responses to acetylcholine (ACh), substance P (SP), bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished. The endothelium-dependent contractions to the nitric oxide synthase inhibitors, NG-nitro-L-arginine (L-NNA; 10-100 microM) and NG-monomethyl-L-arginine (L-NMMA: 10-100 microM), however, were unaffected. 3. Thimerosal (10 microM) did not affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction curve to the thromboxane A2-mimetic, U46619. 4. Both the relaxation response to thimerosal and the selective block of the relaxation responses to stimulated EDRF release were unaffected by either indomethacin (10 microM) or superoxide dismutase (150 u ml-1). 5. L-NNA (100 microM) significantly blocked the relaxation curves to thimerosal and A23187 but not that to SNP.6. Abolition of stimulated EDRF-mediated responses with thimerosal was unlikely to result from maximal and maintained stimulation of EDRF release even when active U46619-induced force had returned to pre-thimerosal levels, since the relaxation curves to glyceryl trinitrate (GTN) and SNP were markedly attenuated in the presence of SNP and GTN respectively when active force was restored with endothelin-1 (ET-1).7. Melittin (1 microM), ionomycin (1 microM) and A23187 (1 microM) each had selective effects on stimulated but not basal EDRF responses, similar to those of thimerosal.8. We propose that stimulated but not 'basal' release of EDRF is dependent on the release of arachidonic acid or one of its non-cyclo-oxygenase metabolites, possibly by Ca2'-dependent activation of phospholipase A2.
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PMID:Thimerosal blocks stimulated but not basal release of endothelium-derived relaxing factor (EDRF) in dog isolated coronary artery. 138 15

The present work was undertaken to determine by immunocytochemical methods which of the putative enteric neurotransmitters are contained in axons supplying the guinea-pig taenia coli and what proportion of axons is accounted for by the presence of these substances. Numerous fibres displayed immunoreactivity for dynorphin (DYN), enkephalin (ENK), gamma-aminobutyric acid (GABA), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in contrast to other gut regions, fibres showing immunoreactivity for gastrin-releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5-hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like immunoreactivity (TH-LI) was present in numerous fibres that disappeared after extrinsic denervation, a procedure that did not detectably affect any of the other major groups of fibres. Simultaneous staining of extrinsically denervated preparations revealed that SP-LI and VIP-LI were located in separate fibres, and ultrastructural studies showed these to be 58% and 33% of intrinsic fibres supplying the muscle. Immunoreactivity for the general marker, neuron-specific enolase, was located in 95-98% of axons. ENK-LI and DYN-LI were in the same axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about 85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI fibres, were reactive for NOS. The results imply that the taenia of the guinea-pig caecum is innervated by two major groups of enteric neurons: (i) excitatory neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases, the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained in a smaller population of intrinsic axons. Even though the taenia represents one of the simplest tissues for examining transmission from enteric neurons to intestinal muscle, it shares some of the complexity of other regions, in that four major axon types supply the muscle and both the enteric excitatory and enteric inhibitory neurons contain multiple transmitters.
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PMID:Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum. 138 81

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82


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