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)

Complications of diabetes include sensory and autonomic neuropathy. The aim of the present paper was to study the degree of sensory and autonomic neuropathy and correlate these findings with the distribution and density of neuropeptidergic nerve fibers in the skin of the forearm of diabetic patients and healthy controls. We investigated 30 diabetics (24 type 1 and 6 type 2) and compared them with 13 healthy controls. There were no differences between the groups with respect to density and distribution of nerve fibers displaying immunoreactivity to the pan-neuronal marker PGP 9.5 and sensory and parasympathetic neuropeptides (substance P, calcitonin gene-related peptide and vasoactive intestinal peptide). By contrast, nerve fibers containing neuropeptide Y, a marker of sympathetic neurons, were reduced in number in the diabetic patients. C-fiber function (measured as the axon-reflex-evoked flare response) became impaired with increasing age in all subjects. The diabetic patients, however, showed a reduced flare compared to age-matched healthy controls. The reduction was particularly prominent in the younger patients (20-50 years). There was a greater reduction of the flare in neuropathic patients than in non-neuropathic patients, but there was no correlation between the degree of functional impairment and the duration of the disease.
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PMID:Innervation of the skin of the forearm in diabetic patients: relation to nerve function. 753 56

The effect of acrylamide intoxication (a widely used model for autonomic neuropathy) on the fluorescence intensity and density of catecholamine- and peptide-containing nerve fibres and tissue content of noradrenaline and the peptides vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P and neuropeptide Y in the enteric nerves of rat ileum was examined. Histochemical and immunohistochemical techniques were used to localize catecholamine- and peptide-containing nerve fibres. The tissue content of noradrenaline was measured using high-performance liquid chromatography, and an enzyme-linked immunosorbent assay technique was used to determine the tissue content of the peptides investigated. Acrylamide intoxication caused a significant decrease in the density of catecholamine-containing nerve fibres and tissue content of noradrenaline in the myenteric plexus of rat ileum. A decrease in tissue content and immunoreactivity of calcitonin gene-related peptide and an increase in vasoactive intestinal polypeptide was seen in the myenteric plexus of ileum from acrylamide-intoxicated rats. In the submucous plexus, the acrylamide treatment caused a decrease in calcitonin gene-related peptide immunoreactivity and an increase in vasoactive intestinal polypeptide and neuropeptide Y immunoreactivity. There was no change in either tissue content or immunoreactivity of substance P in both myenteric and submucous plexuses of the treated rat ileum. These changes have a striking similarity with those found in the enteric nerves of streptozotocin-diabetic rat ileum, suggesting the possible presence of an underlying common mechanism(s) in the development of neuropathic changes in the autonomic nerves of acrylamide-intoxicated and streptozotocin-diabetic rats.
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PMID:Acrylamide-induced neuropathic changes in rat enteric nerves: similarities with effects of streptozotocin-diabetes. 874 Jun 60

Characteristics of the pulpal innervation in teeth obtained from a 4-year-old Asian boy with hereditary sensory and autonomic neuropathy, type II (HSAN) were investigated. Four minimally carious primary teeth were split longitudinally and prepared for either fluorescent immunocytochemistry or electron microscopy. The occurrence and distribution of specific neuropeptides were determined by the use of antisera to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP). The overall innervation of the pulps was visualized using antiserum to protein gene product 9.5; an antiserum to dopamine beta-hydroxylase was used to identify postganglionic sympathetic fibres. Pulpal innervation in HSAN was notably different from that of normal teeth: in comparison with the controls, HSAN teeth had an overall marked reduction in pulpal innervation with an absence of large nerve bundles and the subodontoblastic plexus. CGRP- and SP-immunoreactivity was absent in HSAN specimens and VIP-immunoreactivity was reduced. However, NPY-immunoreactivity appeared to be increased within certain regions of the pulp/dentine complex. In addition, there was evidence of NPY-immunoreactive fibres extending into dentine, a feature not seen in the controls. Electron microscopy revealed an absence of myelinated nerve fibres and a paucity of unmyelinated fibres. CGRP and SP have a well-established role in nociceptive processing and their absence in the HSAN teeth would seem to correspond with the clinical presentation of marked peripheral sensory deficit, characteristic of this condition. An up-regulation of NPY-immunoreactivity has previously been reported in animal teeth following nerve injury and a similar mechanism may have stimulated increased NPY expression in HSAN teeth, but the functional significance of its presence within dentinal nerves is not known.
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PMID:Immunocytochemical and electron-microscopic features of tooth pulp innervation in hereditary sensory and autonomic neuropathy. 971 82

The authors investigated immunocytochemically the innervation of a skin biopsy in a rare case of hereditary sensory and autonomic neuropathy type IV. A few protein gene product 9.5-, growth-associated protein 43-, calcitonin gene-related peptide-, and substance P-immunoreactive nerve fibers were observed in the deeper regions of the dermis. Neuropeptide Y-, nitric oxide-, and vasoactive intestinal polypeptide-immunoreactive fibers were completely absent. Their observations support the hypothesis that the sensory and autonomic defects reported in hereditary sensory and autonomic neuropathy are based on profound developmental alterations of the peripheral nervous system.
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PMID:Cutaneous innervation in hereditary sensory and autonomic neuropathy type IV. 1089 21

Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50-90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium.
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PMID:Nerve growth factor and diabetic neuropathy. 1466 49

Autonomic neuropathy affecting the gastrointestinal system is a major presentation of diabetic neuropathy. Changes in the innervation of gastric mucosa or muscle layers can contribute to gastrointestinal symptoms. The present study investigated this issue by quantitatively analyzing the immunohistochemical patterns of the gastric innervation in rats with streptozotocin (STZ)-induced diabetes. In control rats, calcitonin gene-related peptide (CGRP) and substance P (SP) (+) nerve fibers appeared in the gastric mucosa and muscle layers. Double immunohistochemical staining showed that immunoreactivities for SP and CGRP were co-localized with a pan-neuronal marker protein gene product 9.5. Both SP (+) nerve fibers (p<0.001) and CGRP (+) nerve fibers (p<0.005) were decreased in the gastric mucosa within 4 weeks of diabetes; the reduction persisted throughout 24 weeks. Diabetic rats treated with insulin did not show decrease of SP or CGRP (+) fibers in the mucosa 4 weeks after STZ injection (p>0.05). There was no significant change in SP (+) nerve fibers (p>0.05) or CGRP (+) nerve fibers (p>0.05) of the gastric muscle layers. Reverse transcription-polymerase chain reaction (RT-PCR) showed that the expression levels of SP and CGRP mRNA in the thoracic dorsal root ganglia were similar between diabetic and control animals (p>0.05). Qualitative and quantitative ultrastructural examinations on the gastric mucosa documented unmyelinated nerve degeneration. These results suggest the existence of gastric sensory neuropathy in STZ-induced diabetes, and this pathology provides a foundation for understanding diabetic gastropathy.
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PMID:Depletion of peptidergic innervation in the gastric mucosa of streptozotocin-induced diabetic rats. 1867 69

An incomplete picture has emerged of the complex means by which gallbladder motility is controlled under normal and pathophysiological conditions. In the first part of this review an overall account is presented. The mechanisms of cholecystokinin release, its stimulation by dietary factors and peptides elaborated by both pancreas and small intestine are discussed. The inhibition of cholecystokinin release by bile acids and proteases is also described. In the second part attention is focussed on other peptides affecting motility. These include (a) octreotide, effective for treatment of acromegaly, (b) peptide YY, contributing to a "colonic brake', (c) motilin. associated with interdigestive contractions, analogues of which possibly correct gallbladder hypomotility, and (d) substance P and calcitonin gene-related peptide, which facilitate ganglionic transmission after release from extrinsic sensory neurones and alter gallbladder responses to vagal stimulation. The sympathetic nervous system and diabetes mellitus also influence vagal responses. The former, acting presynaptically, may provide a "brake" to prevent vagal overactivity. The latter could cause hypomotility via autonomic neuropathy, although hyperglycaemia, itself, may play a role. The role of nitric oxide, released from neurones also producing vasoactive intestinal peptide is recognized. Both lengthen muscle, the former producing responses without requiring plasma membrane receptors. Gallbladder motility also changes during pregnancy and stone formation. Progesterone and cholesterol can limit G protein actions, thus impairing contractions. Inflammation is associated with abnormal motility. The production of reactive oxygen metabolites, acting directly or releasing prokinetic prostaglandins, may be responsible. It has been proposed that the gastrointestinal tract may be normally in a state of controlled inflammation, primed to react to harmful challenges.
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PMID:The physiology of the biliary tree. Motility of the gallbladder--part 1. 1986 32

Cardiovascular autonomic neuropathy (CAN), in which patients present with damage of autonomic nerve fibres, is one of the most common complications of diabetes. CAN leads to abnormalities in heart rate and vascular dynamics, which are features of diabetic heart failure. Dysregulated neurohormonal activation, an outcome of diabetic neuropathy, has a significant pathophysiological role in diabetes-associated cardiovascular disease. Key players in neurohormonal activation include cardioprotective neuropeptides and their receptors, such as substance P (SP), neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These neuropeptides are released from the peripheral or autonomic nervous system and have vasoactive properties. They are further implicated in cardiomyocyte hypertrophy, calcium homeostasis, ischaemia-induced angiogenesis, protein kinase C signalling and the renin-angiotensin-aldosterone system. Therefore, dysregulation of the expression of neuropeptides or activation of the neuropeptide signalling pathways can negatively affect cardiac homeostasis. Targeting neuropeptides and their signalling pathways might thus serve as new therapeutic interventions in the treatment of heart failure associated with diabetes. This review discusses how neuropeptide dysregulation in diabetes might affect cardiac functions that contribute to the development of heart failure.
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PMID:Diabetic neuropathy and heart failure: role of neuropeptides. 2183 36

Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in developed and developing nations and over 50% of patients with prolonged stages of disease experience forms of autonomic neuropathy. These patients have symptoms indicating disrupted enteric nervous system function including gastric discomfort, gastroparesis and intestinal dysmotility. Previous assessments have examined enteric neuronal injury within either type 1 diabetic or transgenic type 2 diabetic context. This study aims to assess damage to myenteric neurons within the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2 diabetes, as this disease context is most parallel to the human condition and disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After 8 weeks, the total number of duodenal myenteric neurons and the synaptophysin density index were reduced and transmission electron microscopy showed axonal swelling and loss of neurofilaments and microtubules, suggesting compromised neuronal health. High-fat diet ingestion correlated with a loss of neurons expressing VIP and nNOS but did not affect the expression of ChAT, substance P, calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those with inhibitory nature. This pathology may underlie dysmotility and other negative GI symptoms experienced by human type 2 diabetic and obese patients.
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PMID:High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes. 2388 4


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