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 vascular smooth muscle contractile response to neuropeptide Y (NPY), potassium, noradrenaline, histamine and serotonin was studied in circular segments of isolated vessels in vitro from rabbits with alloxan-induced diabetes mellitus. The injection of alloxan resulted in a marked and maintained increase in serum glucose as early as 1 week after treatment. Four vessel types were examined: abdominal aorta, and renal, left anterior descending coronary and middle cerebral arteries. There was no difference in the contractile response to histamine or serotonin between control and diabetic vessels. However, in the cerebral artery the contractile response to noradrenaline was reduced in the diabetic group, while in the aorta and the renal artery no significant differences were seen. Noradrenaline failed to evoke any contractile response in the coronary arteries in either group. NPY induced strong, concentration-dependent contractions of coronary and cerebral arteries, but did not have any contractile effect per se in aorta or renal arteries, either in control or in alloxan-treated rabbits. The maximal contractile effect and the sensitivity to NPY was significantly less in diabetic coronary and cerebral vessels as compared to control. There was no difference in dilator effect of acetylcholine and substance P between the diabetic animals and the control group in any of the vessel types, indicating that the changed vascular responses to NPY and noradrenaline were not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of NPY and noradrenaline in the peripheral sympathetic nervous system are selectively attenuated in this model of chronic diabetes.
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PMID:Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits. 158 98

Neuropeptides in perivascular nerves of vasa nervorum supplying blood to rat optic, sciatic, vagus and sympathetic chain nerve trunks are differentially vulnerable to streptozotocin (STZ)-induced diabetes. Immunohistochemical analysis of epineurial/perineurial nerve sheaths showed that 8 weeks after induction of diabetes, the density of neuropeptide Y (NPY)-immunoreactive nerve fibres in optic nerve sheaths was increased, while it was decreased in sciatic, vagus and sympathetic nerve sheaths. Vasoactive intestinal polypeptide (VIP)-immunoreactivity was increased in vasa and nervi nervorum of optic, sciatic, vagus and sympathetic chain nerve sheaths. Immunoassay of NPY confirmed increased levels in optic nerve sheaths and showed that substance P and calcitonin gene-related peptide levels increased in sciatic but not optic nerve sheaths. Neuropeptide levels in the intrafascicular nerve fibres were unaffected. This provides further evidence for a disturbance in the autonomic control of blood flow to peripheral and cranial nerve trunks via vasa nervorum in STZ-induced diabetes, which may lead to ischaemic changes, alter local axon reflexes and contribute to the pathogenesis of the disease.
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PMID:Differential vulnerability of neuropeptides in nerves of the vasa nervorum to streptozotocin-induced diabetes. 163 9

The aim of this study was to investigate the possibility that inadequate venous return to the heart in diabetes is the result of a neuropathy which affects autonomic nerves supplying the splanchnic vasculature. Mesenteric veins from rats with streptozotocin-induced diabetes were markedly dilated in vivo compared to veins from control animals. Dilation appeared to be the result of loss of muscle tone rather than hypertrophy or hyperplasia of the vessel wall. Using quantification by image analysis and double-labeling immunohistochemistry on mesenteric veins, significant reductions in the density of nerve plexuses staining for 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) were shown in vessels from diabetic rats compared to controls. No reductions were observed in the density of nerve plexuses stained for the neuronal marker, PGP 9.5, or for substance P (SP), a marker for afferent nerve fibers. These results indicate neurochemical deficits in experimentally induced diabetes which are specific to perivascular noradrenergic nerves and which, within the time-scale of our experiments, do not involve loss of nerve fibers. These deficits may contribute to an increase in venous pooling of blood in the splanchnic vasculature of diabetic rats and thus to inadequate venous return to the heart.
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PMID:Streptozotocin-induced diabetes in rats causes neuronal deficits in tyrosine hydroxylase and 5-hydroxytryptamine specific to mesenteric perivascular sympathetic nerves and without loss of nerve fibers. 167 74

To investigate the possible mechanisms involved in the alterations in sensitivity to pain in diabetic rats, we examined the influence of diabetes induced by streptozotocin (STZ) on the functions of the neuronal systems that contain substance P (SP) within the spinal cord. The threshold for pain perception as determined by a tail-pinch test was significantly reduced in diabetic rats. The levels of SP in the spinal cord from diabetic rats (116.9 +/- 16.3 pmol/g tissue) were significantly lower than those from the control rats (190.2 +/- 14.1 pmol/g tissue). Diabetic rats were found to have a significant increase in the number of binding sites for SP in dorsal spinal cord. The concentrations of binding sites in diabetic rats and in control rats were 102.1 +/- 17.3 fmol/mg protein and 52.6 +/- 6.6 fmol/mg protein, respectively. These data indicate that STZ-induced diabetic rats exhibit supersensitivity to SP in the spinal cord. This may be correlated, in part, with the reduction in the threshold for perception of pain in diabetic animals.
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PMID:Development of supersensitivity to substance P in the spinal cord of the streptozotocin-induced diabetic rats. 169 Sep 1

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.
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PMID:Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum. 169 44

This study examined the effect of treatment of control and streptozotocin-diabetic rats with a mixture of gangliosides, derived from bovine brain, on parameters of axonal transport of substance P-like immunoreactivity (SPLI) and its levels in sciatic nerve and lumbar spinal ganglia. Rats were treated daily (10 mg/kg i.p.) for 28 days and compared with untreated control and diabetic groups. The duration of diabetes was 28 days in both cases. Untreated diabetic rats showed deficits in accumulation of axonally transported SPLI proximal (59% of controls) and distal (34% of controls) to sciatic nerve ligations (left in place for 12 h). Rates of accumulation were unaltered by diabetes. There were small numerical reductions in the SPLI content of unconstricted sciatic nerve and of L4 and L5 dorsal root ganglia in diabetic rats. None of these diabetes-associated changes was altered by ganglioside treatment, nor was there any indication of an effect of gangliosides on substance P in non-diabetic rats. The implications are discussed in relation to the possible pathogenesis of diabetic neuropathy.
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PMID:Axonal transport of substance P-like immunoreactivity in ganglioside-treated diabetic rats. 169 17

We have previously shown depletion of nerves and neuropeptides in skin biopsies of diabetic patients, even in the absence of clinical signs and symptoms of sensory and autonomic neuropathy, but were unable to examine the changes occurring at an early stage of the disease. Therefore, the distribution and relative density of peptide-containing nerves was studied in streptozotocin-treated rats in order to assess the progression of neural changes in the initial stages of diabetes. Skin samples dissected from the lip and footpad of diabetic rats, 2, 4, 8 and 12 weeks after streptozotocin injection and age matched controls were sectioned and were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), and to a general neural marker, protein gene product 9.5 (PGP 9.5). No change was apparent in the distribution or relative density of immunoreactive cutaneous nerve fibres 2, 4 and 8 weeks after streptozotocin treatment. By 12 weeks there was a marked increase in the number of CGRP-immunoreactive fibres present in epidermis and dermis, and of VIP-immunoreactive fibres around sweat glands and blood vessels. A parallel increase was seen in nerves displaying PGP 9.5 immunoreactivity. No differences were detected in nerves immunoreactive for either substance P in the epidermis and dermis, and NPY around blood vessels. The alterations in the peptide immunoreactivities may be similar in the initial stages of human diabetes.
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PMID:Early increase in CGRP- and VIP-immunoreactive nerves in the skin of streptozotocin-induced diabetic rats. 170 1

Recent studies have demonstrated impaired skin hyperaemia to local injury in diabetes mellitus. In order to gain insight into the mechanisms of impaired hyperaemia, dose-response curves to intradermal substance P (25, 50, 100 pmol) and capsaicin (1.0, 2.5, 5.0 nmol) were examined before and after histamine blockade with chlorpheniramine, in 6 patients with uncomplicated Type 1 diabetes and 9 matched control subjects. Skin hyperaemia was measured indirectly as the peak laser Doppler flow in proximity to the area of hyperaemia. The response to the three doses of substance P was significantly lower in diabetic patients (0.37 +/- 0.12 (+/- SD), 0.51 +/- 0.12, 0.67 +/- 0.09 V) than in control subjects (0.57 +/- 0.15, 0.70 +/- 0.19, 0.84 +/- 0.21 V; p less than 0.01). In contrast there was no significant difference in skin hyperaemia to capsaicin between diabetic patients (0.41 +/- 0.07, 0.50 +/- 0.09, 0.59 +/- 0.09 V) and control subjects (0.41 +/- 0.06, 0.52 +/- 0.08, 0.63 +/- 0.07 V). Following chlorpheniramine, the response to capsaicin remained unaltered (0.39 +/- 0.07, 0.51 +/- 0.05, 0.60 +/- 0.07 in diabetic patients and 0.43 +/- 0.08, 0.50 +/- 0.10, 0.63 +/- 0.07 V in control subjects), but there was a significant reduction in hyperaemia to substance P in both patients (20.4 +/- 12.3% reduction, p less than 0.05) and control subjects (20.6 +/- 14.1% reduction, p less than 0.05). It is suggested that impaired skin hyperaemia may represent decreased vascular reactivity to locally released substance P from peripheral nerve fibres.
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PMID:The skin hyperaemic response to local injection of substance P and capsaicin in diabetes mellitus. 170 92

We report herein that streptozotocin (STZ)-induced diabetes selectively alters the nociceptive threshold with respect to noxious mechanical stimuli. Mice were rendered diabetic by an injection of STZ (200 mg/kg, IV). In the tail-pinch test, the latency of the biting response to forceps was significantly decreased in animals with diabetes of 2 weeks and 8 weeks duration as compared to that in age-matched controls. However, the nociceptive threshold, as determined by the tail-flick test, was not significantly altered. The level of substance P in the spinal cord was significantly increased in mice that has been diabetic for 2 weeks, while, there was a significant decrease, as compared to control levels, in level of substance P in mice diabetic for 8 weeks. However, the level of somatostatin was not significantly altered in mice diabetic for either 2 weeks or 8 weeks. These data suggest that STZ-induced diabetes selectively alters a neuronal system that involves substance P but not somatostatin in the spinal cord.
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PMID:Streptozotocin-induced diabetes in mice reduces the nociceptive threshold, as recognized after application of noxious mechanical stimuli but not of thermal stimuli. 171 70

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
Diabetes Res 1990 Sep
PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64


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