Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The perivascular innervation of the superior mesenteric artery and vein was examined using immunohistochemical and immunoassay techniques in rats 8 weeks after induction of diabetes with streptozotocin (STZ). Increased density of innervation and fluorescence intensity was noted for substance P- and calcitonin gene-related peptide-immunoreactive nerves in the diabetic vessels. A slight increase in the density of vasoactive intestinal polypeptide-immunoreactive nerve fibers innervating the mesenteric artery was also noted. However, there was no change in the density of neuropeptide Y- and dopamine beta-hydroxylase-immunoreactive nerve fibers, although the fluorescence intensity of neuropeptide Y-immunoreactive nerve fibers was reduced in diabetic rat vessels. Immunoassays showed that the levels of substance P- and calcitonin gene-related peptide were increased > 10-fold in the diabetic mesenteric vein, while levels of neuropeptide Y and vasoactive intestinal polypeptide were unchanged. In summary, there is a marked increase in nerve fibers containing sensory neuropeptides in mesenteric vessels of STZ-induced diabetic rats, which, in view of the reported impaired sensorimotor function in these vessels, is likely to reflect a neuropathic change.
Diabetes 1996 Feb
PMID:Selective damage to sensorimotor perivascular nerves in the mesenteric vessels of diabetic rats. 854 56

Substance P (SP) is present in perivascular nerves throughout the mammalian vasculature. Reports of diminished SP levels in nerve and gastrointestinal tissues of diabetic rats led us to examine SP-like immunoreactivity (SP-LI) in large arteries by RIA. Six weeks after inducing diabetes with streptozotocin (STZ), SP-LI was measured in the thoracic aorta, abdominal aorta, and the proximal superior mesenteric artery. In diabetics we measured a doubling (P<0.01) of SP-LI in all three artery wall preparations. This finding was verified in a second experiment which included a subset of diabetics treated daily with insulin for the sixth week of the holding period. Again, we measured a two-fold or greater increase of SP-LI (P<0.01-0.05) in arteries from the diabetics and found that insulin treatment significantly reduced SP-LI (P<0.05). In contrast to reports of diminished SP content in other tissues of diabetic rats, our findings demonstrate that the artery wall experiences at least a two-fold increase of SP-LI in the diabetic state. Furthermore, this elevation of SP-LI is reduced by insulin. We speculate that these changes of arterial wall SP-LI may contribute to altered regulation of the vascular system in the diabetic state.
 ...
PMID:Effects of streptozotocin-induced diabetes and insulin treatment on substance P of the rat arterial wall. 861 63

The pathophysiological mechanisms responsible for diabetic gastroparesis remain unclear. Diabetes mellitus occurs spontaneously in 90% of a partially inbred colony of BB/W rats. This animal model resembles human insulin-dependent diabetes and is suitable for investigating the mechanism of diabetic gastroparesis. Diabetic BB/W rats were killed 6 mo after the onset of diabetes. Muscle contraction experiments and [3H]acetylcholine release studies were performed with muscle strips of the gastric body. Biochemical measurements of inositol trisphosphate (IP3) and protein kinase C (PKC) in gastric muscle were performed to characterize abnormalities of the intracellular signal transduction system in gastric myocytes. Circular muscle contractions in response to direct myogenic stimulants, carbachol (10(-7) - 10 (-3)M) or substance P (10(-7) - 10(-5)M), were significantly impaired in diabetic BB/W rats compared with controls. Similarly, muscle contractions in response to NaF (10 mM), a direct stimulant of G proteins, were also impaired in diabetic BB/W rats. In contrast, muscle contractions in response to KCl (25-75 mM) were similar between control and diabetic BB/W rats, indicating normal voltage-dependent Ca2+ entry in muscle strips obtained from diabetics BB/W rats. [3H]acetylcholine release from gastric myenteric plexus in response to electrical transmural stimulation remained intact in diabetic BB/W rats. In separate studies, we demonstrated that carbachol (10(-6) - 10(-4)M) -induced IP3 responses were significantly reduced in diabetic rats compared with control. In addition, there was also impairment of translocation of PKC in diabetic BB/W rats. These observations indicate that myogenic impairment occurred in diabetic BB/W rats. This resulted from altered intracellular signal transduction involving abnormal IP3 production and PKC translocation.
 ...
PMID:Impaired intracellular signal transduction in gastric smooth muscle of diabetic BB/W rats. 863 6

Magnesium(Mg)-deficiency, whether dietary or an effect of a clinical condition such as diabetes, results in a variety of cardiovascular pathologies. Substance P (SP) has been implicated in the induction of cardiac focal inflammatory lesions that occur during Mg-deficiency. Blockade of SP receptors results in a significant reduction in the incidence of lesion formation. In an effort to identify potential endogenous cell populations of the heart, which may play a role in SP-dependent lesion formation, film- and light-microscopic autoradiography were used to map the distribution of specific SP binding sites in frozen sections of the normal rat heart and adjacent great vessels. Binding was assessed with 0.1 nM I-125 Bolton-Hunter labelled SP in the absence (total binding) or presence (non-specific binding) of excess unlabelled SP, prolactin, or L-703,606, a non-peptide antagonist of SP receptors. Film autoradiograms revealed prominent small foci of intense autoradiographic reactions dispersed intermittently around the periphery of the great vessels and coronary arteries, among the interstitial connective tissue of the heart, and along the cusps of the cardiac valves. Excess unlabelled SP caused a significant reduction (97.7% displacement; P < 0.001) in the focal autoradiographic reactions. L-703,606 caused a similar reduction in SP binding (97.3% displacement; P < 0.001), while prolactin had no statistically significant effect on the binding of radiolabelled SP. Light-microscopic autoradiograms revealed that the SP binding sites occurred within clusters of connective tissue cells or in rarely observed parasympathetic ganglia. No evidence was found to suggest the presence of SP receptors on endothelial cells, cardiac muscle fibers, or smooth muscle fibers. The connective tissue cells which bound SP within the heart will likely include types that are susceptible to SP activation and thus may play a role in initiation of the focal inflammation characteristic of Mg-deficiency.
 ...
PMID:Distribution of specific substance P binding sites in the heart and adjacent great vessels of the Wistar white rat. 864 67

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.
 ...
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.
 ...
PMID:Neurotrophins and peripheral neuropathy. 873 Jul 85

Nerve growth factor (NGF) is considered to play a role in neurite outgrowth of small nerve fibres which express its high-affinity receptor, trkA. Nerve regeneration is delayed in diabetes mellitus following an experimental crush injury. In steady-state (i.e., in the absence of axotomy) diabetic rats also show reduced expression of NGF in certain target tissues. This study was designed to measure expression of messenger RNA (mRNA) coding for NGF and its receptors, trkA and p75NGFR, during nerve regeneration and degeneration in rats with streptozotocin-induced diabetes; mRNA coding for preprotachykinin A (the substance P precursor), whose expression is stimulated by NGF, and mRNA for growth-associated protein-43 (GAP-43) were also measured in blots from L4 + L5 (pooled unilaterally) dorsal root ganglia. Unexpectedly, distal stumps of diabetic injured sciatic nerve contained higher levels of NGF mRNA than those of control rats. In ipsilateral dorsal root ganglia of control animals, mRNA for trkA and preprotachykinin A were decreased and GAP-43 mRNA increased after nerve injury; mRNA for p75NGFR was decreased only 3 weeks after nerve transection. In diabetic rats, the levels of all of these mRNA, both in intact and lesioned dorsal root ganglia, were lower than those from control rats. These results suggest that regenerating sensory neurones of diabetic rats receive less NGF support in spite of enhanced NGF mRNA levels in distal stumps compared to non-diabetic rats. Reduced expression of its high-affinity receptor, trkA, in ganglia of diabetic rats might explain this discrepancy.
 ...
PMID:Regenerating sensory neurones of diabetic rats express reduced levels of mRNA for GAP-43, gamma-preprotachykinin and the nerve growth factor receptors, trkA and p75NGFR. 873 48

The aim of the present study was to determine whether diabetes-induced changes in the distribution of enteric neuropeptides, could be prevented in 12-week streptozotocin-diabetic rats, by rigorous control of glycaemia, using daily adminstration of insulin, or an aldose reductase inhibitor (ponalrestat). The pattern of distribution of nerve fibres and cell bodies, containing immunoreactive vasoactive intestinal polypeptide (VIP), galanin (GAL), calcitonin gene-related peptide (CGRP) and substance P was examined in the myenteric plexus of ileum from control, untreated diabetic, insulin-treated diabetic and aldose reductase inhibitor-treated diabetic rats. The increase in VIP- and GAL-like immunoreactivity, seen in the myenteric plexus of untreated diabetic rat ileum, was not present in the myenteric plexus of ileum from insulin- and aldose reductase inhibitor-treated diabetic rats. With CGRP-like immunoreactive fibres, there was a clear decrease in the ileum of untreated diabetic rats. This was prevented by insulin treatment, but aldose reductase inhibitor treatment had no effect. No alterations in substance P-like immunoreactivity were seen in the myenteric plexus of ileum from any of the groups investigated. Generally, the similarity of effect of ponalrestat and insulin on VIP and galanin expression in this study supports a primary effect of insulin via glycaemic control. The dissimilarity of the effect of the two treatments on CGRP expression may imply a neurotrophic effect of insulin, although there are certainly consequences of hyperglycaemia other than exaggerated flux through the polyol pathway.
 ...
PMID:Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and aldose reductase inhibition. 873 9

The effects of streptozotocin-induced diabetes on pituitary neuropeptides were studied. Substance P, dynorphin and beta-endorphin in both pituitary lobes and cholecystokinin and somatostatin in the neurointermediate lobe (NIL) were measured 4 weeks after streptozotocin treatment in adult male rats. There were significant decreases of substance P levels in both the anterior lobe (AL) and NIL, and of cholecystokinin, dynorphin and beta-endorphin in the NIL, whereas the dynorphin content in the AL increased, when values were expressed on a per-lobe basis. On a per-milligram-protein basis, however, only beta-endorphin in the NIL showed a significant decrease, while AL beta-endorphin and dynorphin were increased. Correlated with these changes were a drastic decrease in the serum insulin level and a marked increase in serum glucose and corticosterone levels. All these changes were reversible with insulin treatment. It is suggested that the decrease in NIL contents of neuropeptides demonstrated (except for beta-endorphin) might be due to mechanisms other than a change in synthesis.
 ...
PMID:Pituitary contents of beta-endorphin, dynorphin, substance P, cholecystokinin and somatostatin in rats with streptozotocin-induced diabetes. 873 22

Complications arising from diabetes mellitus include hormonal dysfunctions such as impairment in the regulation of gonadatroph and corticotroph secretion. Preprotachykinin (PPT) mRNA encoding the peptide substance P (SP), has been localized in the anterior pituitary. The goal of this study was to determine if streptozotocin (STZ)-induced diabetes affects the SP content or PPT mRNA level in the pituitary of male rats. We injected STZ (55 mg/kg) to 6-week-old rats which developed hyperglycemia (blood glucose > 400 mg/dl) by 6 weeks post-injection. SP-like immunoreactivity in the pituitary dropped 54%. In situ hybridization was performed using a PPT-specific oligonucleotide with signal intensity differences semi-quantified using an image analysis system. Normal pituitary had a regional distribution of PPT mRNA, with no detectable signal in the posterior or intermediate lobes, while the anterior lobe displayed a distinctive pattern of labeled cells arranged in clusters. In diabetic rats there was a 23% decrease in the PPT-mRNA hybridization signal compared to controls (P < 0.05). The changes observed in PPT gene expression and SP content may be additional factors participating in the hormonal complications seen in diabetes mellitus.
 ...
PMID:Streptozotocin-induced diabetes produces a decrease in pituitary substance P content and preprotachykinin mRNA. 883 Aug 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>