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 density and distribution of reactivity for two lectins (soybean agglutinin (SBA) and RL-29), growth associated protein-43 (GAP-43) and the neuropeptides substance P and calcitonin gene-related peptide were analyzed in the spinal cord dorsal horn of rats with an experimental peripheral neuropathy. Twenty-eight days postsurgery, the density of label for RL-29 and GAP-43 was increased in laminae I and II on the experimental compared to the control side. In contrast, the density of neuropeptide label was decreased in the same region. Furthermore, on the experimental side, the distribution of both SBA and RL-29 reactivity was increased, extending into lamina III. We hypothesize that the increases in density and distribution of reactivity for the lectins and GAP-43, as well as the decreases in neuropeptide reactivity, reflect injury-induced regenerative changes in primary afferent terminals.
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PMID:Changes in lectin, GAP-43 and neuropeptide staining in the rat superficial dorsal horn following experimental peripheral neuropathy. 172 99

Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut. 259 79

Histochemical, immunohistochemical and neurochemical techniques were used to examine the innervation of epineurial nerve sheaths and fascicular nerve bundles of human sural and optic nerves from controls and patients with peripheral neuropathy due to diabetes or alcoholism. The normal distribution of autonomic nerves in both nerve trunk sheaths consisted of a dense innervation by noradrenaline (NA)-containing nerves of the vasa nervorum, together with some fibres in the nervi nervorum. Intrafascicular NA-containing nerves were only present in the sural nerve. Vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerves also innervated the vasa nervorum and nervi nervorum of the nerve sheaths, although their density was considerably less. Substance P (SP)-containing nerves were sparse and primarily intrafascicular. Neurochemical assays for NA, VIP, NPY and SP in fascicular and epineurial preparations from the sural and optic nerves confirmed the light microscopical observations. Post mortem delay significantly affected the NA levels in the sural nerve but not in the optic nerve while the NA fascicular/epineurial ratio for the sural nerve was independent of this factor. Age, sex and the presence of alcohol at time of death had no effect on transmitter levels in normal sural nerves. In the optic nerve fascicles NA levels were higher in females than in males. In patients with peripheral neuropathy there was a significant reduction in the SP fascicular/epineurial ratio in both the optic nerve, which was histologically normal, and in the sural nerve, where there was evidence of neuropathy. The NA fascicular/epineurial ratio was also significantly reduced in the sural nerve from patients with peripheral neuropathy with a possible greater effect in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Innervation of normal human sural and optic nerves by noradrenaline- and peptide-containing nervi vasorum and nervorum: effect of diabetes and alcoholism. 751 81

The extranuclear endogenous mono-ADP-ribosylation of proteins in cellular fractions from retinas of control and diabetic rats was studied. At least six proteins were ADP-ribosylated in the crude extract, membrane and cytosolic fractions from control preparations, whereas in diabetic rats the number of labeled proteins and the extent of labeling were highly reduced. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations of the extent of ADP-ribosylation of the 38 K cytosolic, 39 K, 40 K membrane and 39 K, 41 K and 42 K crude extract proteins. These data suggest a hyperactivity of extranuclear endogenous protein mono-ADP-ribosylation in the diabetic rat retina, and that treatment with silybin inhibits such enzyme activity, thus improving the extent of ADP-ribosylation. Sciatic nerve axonal transport of substance P was reduced markedly in diabetic rats, and inhibition of mono-ADP-ribosylation with silybin prevented such a loss in spite of high blood glucose levels. These results suggest that the abnormal endogenous ADP-ribosylation of proteins might play a role in the onset of diabetic peripheral neuropathy and its inhibition may represent a novel pharmacological approach to the treatment of diabetes complications.
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PMID:Experimental diabetic neuropathy. Inhibition of protein mono-ADP-ribosylation prevents reduction of substance P axonal transport. 754 40

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.
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PMID:The effects of vasoactive intestinal polypeptide and substance P on methacholine-induced sweating and vascular flare in diabetic neuropathy. 754 18

An animal model of peripheral neuropathy resulting in a unilateral hyperalgesia has recently been developed. The N-methyl-D-aspartate (NMDA) antagonist MK-801 reduces the thermal hyperalgesia observed in this model. The goal of the present study was to determine whether the immunohistochemical changes in dorsal horn peptides shown by neuropathic animals could also be modified by MK-801. Changes in immunostaining densities of substance P (SP) and calcitonin gene-related peptide (CGRP) within the spinal cord of untreated (reference population) neuropathic rats and that of neuropathic rats treated for 7 days with MK-801 were quantified and compared. The reference neuropathic animals demonstrated thermal hyperalgesia and an ipsilateral decrease in SP staining density without an accompanying change in CGRP staining density. MK-801-treated animals showed a dose-dependent attenuation of the thermal hyperalgesia. The expected ipsilateral decrease in SP was prevented in neuropathic animals treated with a low dose (0.5 mg/kg) of MK-801, while a higher dose of MK-801 (1 mg/kg) resulted in an increase in SP staining ipsilateral to the injury. MK-801 treatment in naive rats caused a global increase in both SP and CGRP staining in the dorsal horn. However, this global increase failed to mask the changes in staining density in neuropathic animals following MK-801 treatment. The results suggest a functional interaction between excitatory amino acids (EAAs) and SP, with activation of NMDA receptors mediating depletion of SP in neuropathic animals. It is suggested that SP-containing interneurons are a target of the EAAs in the dorsal horn.
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PMID:Quantitative analysis of substance P and calcitonin gene-related peptide immunohistochemical staining in the dorsal horn of neuropathic MK-801-treated rats. 768 39

Glutamate is a major neurotransmitter of fine afferent fibers to the spinal cord. Neuropeptides are also released by the same fibers. We explored, by quantitative immunocytochemistry, the effects of two experimental manipulations of peripheral nerves on the levels of these two classes of mediators. Glutamate levels in the superficial dorsal horn of rats increased after chronic loose ligature of the sciatic nerve, a model for hyperpathic peripheral neuropathy. A similar increase was observed acutely, after stimulation of C fibers, but not A fibers, in the sciatic nerve. In contrast, immunostaining for substance P and calcitonin gene-related peptide decreased in the same region with both manipulations. The decrease in immunocytochemical levels of peptides is in agreement with previous observations and can result from activity-related depletion. We propose that the increase in glutamate levels reflects differences in the regulation and kinetics of amino acid versus peptide neuromediators.
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PMID:Glutamate immunocytochemistry in the dorsal horn after injury or stimulation of the sciatic nerve of rats. 809 61

Endogenous nerve growth factor (NGF) levels were studied in patients with nerve trauma, diabetes mellitus and leprosy, the most common causes of human peripheral neuropathy. In diabetics, there was an early length-dependent dysfunction of small-diameter sensory fibres, with depletion of skin NGF and the sensory neuropeptide substance P. The NGF depletion correlated significantly with decreased skin axon-reflex vasodilatation, which is mediated by small sensory fibres at least partly via substance P release. Immunostaining showed depletion of NGF in keratinocytes in diabetic skin. In injured nerves, NGF levels were reduced when compared to intact nerve, except acutely distal to injury; NGF-immunostaining was seen in Schwann cells in distal segments, including neuromas. NGF levels were decreased in leprosy-affected skin and nerve. The role of neurotrophins in the rational treatment of human neuropathies is discussed e.g. loss of nociception and axon-reflex vasodilatation contribute to skin ulceration, a major and serious complication, for which NGF may provide prophylaxis.
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PMID:Neurotrophins and peripheral neuropathy. 873 Jul 84

The most common form of peripheral neuropathy is that associated with diabetes mellitus. In rodent models of diabetes there are expression deficits in nerve growth factor (NGF) and in its high-affinity receptor, trkA, leading to decreased retrograde axonal transport of NGF and decreased support of NGF-dependent sensory neurons, with reduced expression of their neuropeptides, substance P and calcitonin gene-related peptide (CGRP). Treatment of diabetic rats with intensive insulin normalized these deficits and treatment with exogenous NGF caused dose-related increases, giving levels of NGF and neuropeptides which were greater than those of controls. Neurotrophin-3 (NT-3) mRNA was also deficient in leg muscle from diabetic rats and administration of recombinant NT-3 to diabetic rats increased the conduction velocity of sensory nerves without affecting motor conduction velocity. These findings implicate deficient neurotrophic support in diabetic neuropathy and suggest that its correction should be a paramount therapeutic target.
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PMID:Neurotrophins and peripheral neuropathy. 873 Jul 85

The chronic constriction injury (CCI) is an animal model of an experimental peripheral neuropathy. In this model, a mononeuropathy is produced by loosely ligating the left sciatic nerve of the rat with chromic gut suture (Bennett and Xie 1988). Maves et al. (1993) have proposed that chemical constituents of chromic gut suture influence the behavioral changes of rats with the CCI. Considering their results, we became interested in evaluating whether the type of suture material used to produce the CCI also affected spinal levels of calcitonin-gene-related peptide immunoreactivity (CGRP-ir) and substance P immunoreactivity (SP-ir), peptides that are associated with small primary afferent neurons. Using methods of radioimmunoassay (RIA), we measured levels of CGRP-ir and SP-ir in the dorsal quadrants of approximately the lumbar 4-5 (L4-L5) spinal segments of rats with a CCI induced using polyglactin (Vicryl), plain gut, or chromic gut suture. We observed bilateral decreases in CGRP-ir and SP-ir 60 days after a CCI induced with chromic gut suture, but no changes in peptide levels after a CCI induced with either polyglactin or plain gut suture. These results suggest two possibilities: (1) chromic gut suture, when used to produce the CCI, has more than just a constrictive effect on the sciatic nerve, and/or (2) different suture materials produce changes in CGRP-ir and SP-ir with a differential time-course. Our experiments are unable to distinguish between these two possibilities.
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PMID:Chromic gut suture reduces calcitonin-gene-related peptide and substance P levels in the spinal cord following chronic constriction injury in the rat. 878 15


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