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)

This study examined the effect of trophic factor supplementation [TFS; bovine neutrophil peptide-1 (bactenecin), 1 mg/L; substance P, 2.5 mg/L; nerve growth factor, 20 microg/L; epidermal growth factor, 10 microg/L; insulin-like growth factor-1, 10 microg/L] during cold storage with UW lactobionate solution. Dogs transplanted with kidneys stored for 4days in TFS-UW had significantly lower peak serum creatinine values (mean 2.9 +/- 0.2mg/dL) and returned to normal values faster (6 days) than kidneys stored for 3days in unmodified UW solution (4.2 +/- 0.3 mg/dL and 14 days, respectively). Kidneys stored for 5days in TFS-UW (mean peak creatinine 3.7 +/- 0.3) functioned equivalently to kidneys stored for 3days and better than kidneys stored for 4 days in UW alone. Dogs with kidneys stored for 6days in TFS-UW had mean peak creatinines of 5.7 +/- 0.4 mg/dL. These returned to normal creatinine values in 14 days, equal to 3-day stored and significantly better than kidneys stored for 4days in UW alone (20days recovery time). This study shows trophic factor deprivation appears to be a critical mechanism of injury in organ preservation with current synthetic storage media, and marks the initial development of a synthetic biologically active preservation solution, the next generation of preservation media.
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PMID:Successful six-day kidney preservation using trophic factor supplemented media and simple cold storage. 1224 92

Serum-free preservation media such as University of Wisconsin (UW) may cause tissue damage through trophic factor (TF) deprivation. This study evaluated whether the addition of TFs to UW solution improves liver graft quality after extended cold preservation time in pigs. UW solution was supplemented with epidermal growth factor, insulin-like growth factor-1, nerve growth factor-beta, bactenecin, and substance P to create TF-supplemented (TFS) UW. Orthotopic liver transplantation was performed after 18 hr of static cold storage at 4 degrees C in UW (n=7) or TFS-UW (n=7) solution. Recipients of grafts preserved with TFS-UW demonstrated significantly better 5-day survival (57%) than those preserved with UW alone (14%) (P<0.05). Adenosine triphosphate content in grafts preserved in TFS-UW was significantly higher than in grafts preserved in UW (17.4+/-5.0 vs. 4.8+/-1.2 nmol/mg protein, respectively) (P<0.05). This study showed that the addition of TFs to UW solution allowed a significant extension of cold ischemic time in pigs.
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PMID:Improved survival of orthotopic liver allograft in swine by addition of trophic factors to University of Wisconsin solution. 1474 97

This study was performed to assess cutaneous nerve fibre loss in conjunction with temperature and sweating dysfunction in familial dysautonomia (FD). In ten FD patients, we determined warm and cold thresholds at the calf and shoulder, and sweating in response to acetylcholine iontophoresis over the calf and forearm. Punch skin biopsies from calf and back were immunostained and imaged to assess nerve fibre density and neuropeptide content. Mean temperature thresholds and baseline sweat rate were elevated in the patients, while total sweat volume and response time did not differ from controls. The average density of epidermal nerve fibres was greatly diminished in the calf and back. There was also severe nerve loss from the subepidermal neural plexus (SNP) and deep dermis. The few sweat glands present within the biopsies had had reduced innervation density. Substance P immunoreactive (-ir) and calcitonin gene related peptide-ir (CGRP-ir) were virtually absent, but vasoactive intestinal peptide-ir (VIP-ir) nerves were present in the SNP. Empty Schwann cell sheaths were observed. Temperature perception was more impaired than sweating. Epidermal nerve fibre density was found to be profoundly reduced in FD. Decreased SP and CGRP-ir nerves suggest that the FD gene mutation causes secondary neurotransmitter depletions. Empty Schwann cell sheaths and VIP-ir nerves suggest active denervation and regeneration.
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PMID:Assessing function and pathology in familial dysautonomia: assessment of temperature perception, sweating and cutaneous innervation. 1524 Apr 36

Lamina I of the spinal cord contains many projection neurons: the majority of these are activated by noxious stimulation, although some respond to other stimuli, such as innocuous cooling. In the rat, approximately 80% of lamina I projection neurons express the neurokinin 1 (NK1) receptor, on which substance P acts. Lamina I neurons can be classified into three main morphological classes: pyramidal, fusiform and multipolar cells. It has been reported that in the cat, pyramidal cells respond to innocuous cooling, and whilst both fusiform and multipolar cells are activated by noxious mechanical and heat stimuli, only cells in the latter group respond to noxious cold [Nat Neurosci 1 (1998) 218]. However, we have previously shown that NK1 receptor-immunoreactive projection neurons belonging to each morphological class are equally likely to up-regulate the transcription factor Fos after noxious chemical stimulation, and that the density of innervation by substance P-containing (nociceptive) afferents is similar for cells of each type [J Neurosci 22 (2002) 4103]. This suggests that the morphological-physiological correlation that has been reported in the cat may not apply in the rat. We have tested this further by examining Fos expression in lamina I spinoparabrachial neurons in the rat after application of noxious heat or noxious cold stimuli under general anesthesia. Following noxious heat, 57-69% of NK1 receptor-immunoreactive spinoparabrachial neurons expressed Fos, and the proportion did not differ significantly between morphological groups. However, after noxious cold stimulation Fos was present in 63% of multipolar neurons, but only 19-26% of fusiform or pyramidal cells. These results suggest that although most NK1 receptor-expressing spinoparabrachial neurons are activated by noxious stimuli, responsiveness to noxious cold is significantly more common in those of the multipolar type. There therefore appears to be a correlation between morphology and function for lamina I projection neurons in the rat.
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PMID:Fos induction in lamina I projection neurons in response to noxious thermal stimuli. 1568 Jul 4

Using models of airway diseases, our understanding of the role of tachykinins and kinins in airway pathophysiology has been greatly enhanced by the recent development of a large series of peptide, peptoid and non-peptide antagonists for tachykinin and kinin receptors. This article reviews the experimental findings of the contribution of kinins and tachykinins and their respective receptors, in models of airway inflammation in response to agents known to trigger or worsen asthma attacks, such as antigen and cold air. Some new antagonists, mostly of a non-peptide nature, exhibit excellent pharmacodynamic and pharmacokinetic profiles; a brief account of early clinical studies in which they have been used is also given.
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PMID:Tachykinins and kinins in airway allergy. 1599 96

Not all neuropathic pain patients gain relief from current therapies that include the anticonvulsant, gabapentin, thought to modulate calcium channel function. We report a neural circuit that is permissive for the effectiveness of gabapentin. Substance P-saporin (SP-SAP) was used to selectively ablate superficial dorsal horn neurons expressing the neurokinin-1 receptor for substance P. These neurons project to the brain as shown by retrograde labelling and engage descending brainstem serotonergic influences that enhance spinal excitability via a facilitatory action on 5HT(3) receptors. We show the integrity of this pathway following nerve injury contributes to the behavioural allodynia, neuronal plasticity of deep dorsal horn neurons and the injury-specific actions of gabapentin. Thus SP-SAP attenuated the tactile and cold hypersensitivity and abnormal neuronal coding (including spontaneous activity, expansion of receptive field size) seen after spinal nerve ligation. Furthermore the powerful actions of gabapentin after neuropathy were blocked by either ablation of NK-1 expressing neurones or 5HT(3) receptor antagonism using ondansetron. Remarkably, 5HT(3) receptor activation provided a state-dependency (independent of that produced by neuropathy) allowing GBP to powerfully inhibit in normal uninjured animals. This circuit is therefore a crucial determinant of the abnormal neuronal and behavioural manifestations of neuropathy and importantly, the efficacy of gabapentin. As this spino-bulbo-spinal circuit contacts areas of the brain implicated in the affective components of pain, this loop may represent a route by which emotions can influence the degree of pain in a patient, as well as the effectiveness of the drug treatment. These hypotheses are testable in patients.
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PMID:Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. 1615 May 46

Substance P is a neuropeptide involved in inflammation, immune regulation and stress response. Stress may induce bladder damage by stimulating inflammatory response such as mast cell activation. We here examined the role substance P during stress-induced mast cell degranulation and urothelial injury in rat bladder. Adult Sprague-Dawley rats (200-270 g) were either exposed to cold-immobilization stress or substance P (SP) intracerebroventricularly. Different doses of substance P receptor (NK1R) antagonist CP 99994 were administered peripherally or centrally before the stress exposure. From each group, samples of the bladder were examined with light and electron microscope. Stress- and SP-injected centrally, increased the number of both granulated and degranulated mast cells. Ultrastructurally, urothelial degeneration with vacuolization in the cytoplasm and dilated intercellular spaces were seen. Both central and peripheral injection of CP 99994 prevented stress-induced urothelial degeneration as well as stress-induced mast cell degranulation. In conclusion, centrally and peripherally released substance P is involved in stress-induced bladder damage. Inhibition of NK1R prevents stress-induced pathological changes of urinary bladder and NK1R antagonist can be considered for the treatment of inflammatory bladder diseases.
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PMID:Inhibition of substance P activity prevents stress-induced bladder damage. 1623 38

The airway nerve has gained importance in the field of respiratory research as it is known to have the capacity to release numerous mediators which can cause pulmonary effects in the airways. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and cold dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. SP is synthesized in cell bodies of airway neurons of the trigeminal, jugulare and nodose ganglia. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and an angiotensin-converting enzyme. Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors. Recently, new tachykinins such as virokinin and hemokinin were identified and characterised. Different aspects of the neurogenic inflammation have been well studied in animal models of allergic airway inflammation, but only little is known about the role of neurogenic airway inflammation in human diseases. To address the precise role of tachykinins and airway sensory nerves in human asthma und COPD, experiments on sensory nerve sensitisation and neuro-immune interaction have to be carried out in future studies.
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PMID:[Airway sensory nerve and tachykinins in asthma and COPD]. 1646 47

A familial case of limb pain is described. Frequent vascular pain appeared during early childhood in affected individuals, often with predominance in the lower extremities. This pain subsided in patients during adolescence, when they began to suffer from typical migraine. The limb pain was moderate to severe, and refractory to analgesic and anti-migraine medications. Limb temperature was cold at the onset of pain, and became warm during the painful attacks. Plasma substance P and calcitonin gene-related peptide were elevated during the episodic pain. We propose this condition is a new precursor etiology of migraine, with possible autosomal dominant inheritance.
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PMID:Familial limb pain in childhood: unusual manifestation of migraine? 1676 48

The modulatory effect of ionophoretic application of substance P to the skin on the formation of the cold-triggered thermal protection reactions depends on the rate of cooling. During rapid cooling substance P enhances heat production, while during slow cooling it promotes constriction of skin blood vessels aimed at reduction of heat emission.
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PMID:Effect of substance P on thermoregulation parameters during different cooling modes. 1736 52


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