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)

1. Neurogenic vasoactive responses in rat skin were investigated following 8 weeks of streptozotocin-induced diabetes to determine the effect of diabetes and of treatment with insulin and nerve growth factor (NGF) treatment. 2. Diabetic rats were divided into three groups: untreated; insulin (4 IU day(-1) by s.c. implant weeks 4-8) treated; Nerve Growth Factor, NGF, (0.2 mg kg(-1) three times weekly, weeks 4-8) treated. A fourth group served as a non-diabetic control. 3. Electrical stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 30 s) increased blood flow in the ipsilateral paw skin, as measured by laser Doppler flowmetry. The peak increase was similar between groups, but the time taken for flow to return to a steady baseline was significantly (P < 0.01) reduced in untreated diabetic rats, when compared with non-diabetic controls, but not significantly reduced in the insulin- or NGF-treated diabetic groups. 4. A second stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 5 min) produced plasma extravasation, measured by the extravascular accumulation of 125I-albumin, in the skin. Plasma extravasation was significantly attenuated (P < 0.001) in the untreated diabetic group, but not the insulin-treated group, compared to non-diabetic controls. Plasma extravasation was present, though reduced, in the NGF-treated group. 5. Plasma extravasation induced by intradermal injections of substance P with and without CGRP was similar in all groups indicating no decrease in vascular responsiveness to exogenously applied neuropeptides. The results suggest that release of neuropeptides is diminished in diabetes and that treatment with either insulin or NGF can restore neurogenic microvascular vasoactive responses towards normal.
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PMID:Neurogenic cutaneous vasodilatation and plasma extravasation in diabetic rats: effect of insulin and nerve growth factor. 972 73

A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.
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PMID:Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord. 974 64

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P < 0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P < 0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NFG, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes--a mechanism that might participate in iritis.
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PMID:Stimulation of nerve growth-factor and substance P expression in the iris-trigeminal axis of diabetic rats--involvement of oxidative stress and effects of aldose reductase inhibition. 974 8

The goal of this study was to test the hypothesis that the synthesis/release of hydroxyl radical accounts for impaired nitric oxide synthase-dependent dilatation of the basilar artery during diabetes mellitus. We measured the diameter of the basilar artery in vivo in nondiabetic and diabetic rats (streptozotocin, 50-60 mg/kg ip) in response to nitric oxide synthase-dependent agonists (acetylcholine and substance P) and a nitric oxide synthase-independent agonist (nitroglycerin). Reactivity of the basilar artery was measured in untreated nondiabetic and diabetic rats and in nondiabetic and diabetic rats treated with a daily intraperitoneal injection of dimethylthiourea (DMTU; 50 mg/kg). Injection of DMTU was started 48 h after injection of streptozotocin and was continued throughout the diabetic period (3-4 wk). Topical application of acetylcholine (0.1, 1.0, and 10 microM) and substance P (0.1 and 1.0 microM) produced similar dilatation of the basilar artery in untreated and DMTU-treated nondiabetic rats. In untreated diabetic rats, the magnitude of vasodilation produced by acetylcholine and substance P was significantly less than in untreated nondiabetic rats. However, in DMTU-treated diabetic rats, dilatation of the basilar artery in response to acetylcholine and substance P was similar to that observed in nondiabetic rats. Dilatation of the basilar artery in response to nitroglycerin was similar in untreated and DMTU-treated nondiabetic and diabetic rats. These findings suggest that impaired nitric oxide synthase-dependent dilatation of the basilar artery during diabetes mellitus may be related to the synthesis/release of hydroxyl radical.
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PMID:Treatment with dimethylthiourea prevents impaired dilatation of the basilar artery during diabetes mellitus. 984 17

We studied the release of somatostatin, calcitonin gene-related peptide (CGRP) and substance P in response to electrical field stimulation from isolated tracheas of rats following 4 weeks of streptozotocin (50 mg/kg i.v.)-induced diabetes. Field stimulation (40 V, 0.1 ms, 10 Hz for 120 s) increased the release of somatostatin, CGRP and substance P from the baseline 0.18+/-0.029, 0.17+/-0.027, and 1.77+/-0.086 to 0.51+/-0.022, 0.69+/-0.115, and 5.96+/-0.377 in control preparations and 0.31+/-0.081, 0.41+/-0.142, and 3.14+/-0.443 fmol/mg wet tissue weight in preparations from diabetic rats as measured by radioimmunoassay (control vs. diabetic P<0.01 for each). The results show a simultaneous decrease in release of the three sensory neuropeptides and an enhanced plasma somatostatin level in rats with streptozotocin-induced diabetes.
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PMID:Decreased sensory neuropeptide release from trachea of rats with streptozotocin-induced diabetes. 1020 82

Our aim was to determine sites of substance P binding in the gut of the BB rat and examine changes in SP binding in the diabetic rat, over time. Specific binding of [125I]substance P was localized in sections of nondiabetic gut using emulsion autoradiography and quantitated in diabetic and nondiabetic gut using film autoradiography. High levels of SP binding were located in esophageal muscularis mucosa, circular muscle of the stomach and colon, deep muscular plexus, and in the circular muscle adjacent to the plexus in the ileum. The myenteric plexus demonstrated moderate to high levels of binding. Specific binding increased in the antrum and pylorus at three weeks and in the jejunum and distal colon at four weeks of diabetes but decreased in the distal ileum at two to four weeks of diabetes. Changes persisted at four to six months. These results contribute to understanding changes in the control of intestinal motility in diabetes.
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PMID:Substance P binding in gastrointestinal tract of nondiabetic BB rat and changes in diabetic BB rat over time. 1021 33

This study examines whether there is a change in the pattern of distribution of cholecystokinin-octapeptide (CCK-8), calcitonin-gene-related peptide (CGRP), neuropeptide-Y (NPY), substance P (SP) and vasoactive intestinal polypeptide (VIP) in the pancreas of streptozotocin (STZ)-diabetic (host) rats after subcutaneous pancreatic transplantation. Varicose CCK-8-immunopositive nerve fibres were observed in the wall of blood vessels of both normal and diabetic host pancreata. The density of CCK-8-immunoreactive varicose nerve fibres appeared to have increased in host rat pancreas. CGRP was demonstrated in many nerve fibres located in the wall of blood vessels of both normal and host pancreas. CGRP, however, seemed to be better expressed in the nerves of host pancreas when compared to normal. The pancreata of both normal and diabetic (host) rats contained numerous NPY-immunopositive varicose nerve fibres located in the wall of blood vessels. SP was demonstrated in neurons located in the interlobular areas of normal tissue and in fine varicose nerve fibres of the interacinar region of the pancreas of STZ-induced diabetic rats with SPTG. In normal pancreatic tissue, VIP-immunopositive nerve fibres were observed in all areas of the pancreas. VIP-positive nerve fibres were still discernible especially in the interacinar regions of the pancreas of host rats. In conclusion, the pattern of distribution and density of NPY, SP and VIP in the pancreas of STZ-induced diabetic rats with SPTG is similar to that observed in normal pancreas, but the expression of CGRP and CCK-8 seemed to have increased as a result of transplantation and or diabetes.
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PMID:Effect of subcutaneous pancreatic tissue transplants on streptozotocin-induced diabetes in rats. III. Distribution of neuropeptides in normal and diabetic (host) pancreas. 1036 89

We have recently demonstrated that prosaposin is a neurotrophic and myelinotrophic factor with the active trophic sequence located at the N-terminal region of the saposin C domain. There are also reports that prosaposin mRNA is increased distal to a physical nerve injury and that exogenous prosaposin treatment induces subsequent neuronal sprouting, suggesting involvement in repair processes. In the present study, we show that prosaposin mRNA is significantly (p < 0.05) elevated in the peripheral nerve of streptozotocin-diabetic rats, a model of insulin-deficient diabetes in which nerve injury arises from the metabolic trauma of hyperglycemia and its consequences. A 14 amino acid peptide derived from the neurotrophic region of prosaposin prevented the development of deficits in both large and small fiber function caused by diabetes in rats. The dose-dependent prevention of nerve conduction slowing by TX 14(A) was accompanied by preservation of axonal caliber and sodium-potassium ATPase activity, while prevention of thermal hypoalgesia was associated with attenuation of the decline in nerve substance P levels. It is concluded that nerve subject to the metabolic injury of uncontrolled diabetes responds by increasing prosaposin gene expression, and that prosaposin-derived neurotrophic peptides may provide a novel therapeutic approach to treatment of diabetic and other peripheral neuropathies.
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PMID:Prosaposin gene expression and the efficacy of a prosaposin-derived peptide in preventing structural and functional disorders of peripheral nerve in diabetic rats. 1037 53

Diabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of mRNA expression in specific neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%. Conversely, the mRNA expression of low-affinity neurotrophin receptor p75 was increased. At birth, BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of BDNF and p75 mRNAs and an increase of NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of IGF-I, while we observed a partial impairment of substance P axonal transport at postnatal day 28. Treatment of diabetic mothers with silybin, a flavonoid with antioxidant properties, prevented most of the changes in neurotrophic factor expression and substance P axonal transport with no effects on hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence neurotrophic factor synthesis in target territories during development. In addition, these data suggest that nervous system abnormalities observed in diabetic embryopathy may also derive by insufficient neurotrophic factor biosynthesis involving sequentially NGF in the embryo and BDNF and IGF-I in the early postnatal days. Insulin treatment of diabetic mothers normalized hyperglycemia and body growth, with consequent regular embryonic and postnatal development.
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PMID:Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: protective action of antioxidant treatment. 1044 Sep 1

Substance P (SP) and calcitonin gene-related peptide (CGRP) constitute the main sensory peptides in the trigeminal ganglion (TG). The objective of this study was to characterize peptidergic changes in the streptozotocin-induced diabetes mellitus rat model both quantitatively and qualitatively. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) and the levels of SP and CGRP were measured by means of radioimmunoassay (RIA) in a time-dependent manner. Peptide immunoreactivities were characterized by high pressure liquid chromatography (HPLC). The expression of both neuropeptides was examined 5 weeks after streptozotocin injection using in situ hybridization with 35S-labelled oligonucleotides. Saline-injected rats served as controls. SP was significantly decreased in the diabetic rat TG, i.e. , a 44.6% (+/-10.9) decrease after 1 week, 40.2% (+/-11.8) after 3 weeks and 72.3% (+/-14.6) after 5 weeks. CGRP was decreased only after 5 weeks (19.6% decrease +/-3.9), whereas at later stages, both peptide levels returned to normal values. HPLC revealed one major peak coeluting with the synthetic peptides. By using in situ hybridization, a significantly increased signal of both peptide-encoding mRNAs was found (43.8%), which seems to act to restore a diabetes-associated depletion of neuropeptides in the diabetic rat TG. The decreased SP- and CGRP levels in the diabetic rat TG reflect a diabetes-associated deficit which may be clinically relevant. Diabetes mellitus is associated with a variety of ocular complications, even corneal complications, including decreased corneal sensitivity, which in many ways resemble those after interruption of the normal trophic innervation of the eye. Our results point to reduced availability of neuropeptides for corneal innervation and may thus support the idea of a partial loss of trophic influences from the trigeminal nerve in diabetics.
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PMID:The effect of streptozotocin-induced diabetes mellitus on substance P and calcitonin gene-related peptide expression in the rat trigeminal ganglion. 1052 98


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