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 presence and distribution of the presumed pan-neural marker protein gene product 9.5 (PGP)- and peptide-immunoreactive (ir) nerve fibers in alveolar walls of various species was investigated by light microscopic single and double staining immunohistochemistry. PGP-, tachykinin (TK)-, and calcitonin gene-related peptide (CRGP)-ir fibers were sparsely distributed in a similar pattern in alveolar walls of all species investigated. No vasoactive intestinal peptide-, peptide histidine isoleucine-, galanin-, and opioid-ir nerve fibers could be detected. PGP-ir fibers outnumbered those staining for TKs and CGRP. There was partial coexistence of PGP and TK as well as of TK and CRGP. PGP-, TK-, and CGRP-ir fibers were in close spatial relationships to the cells building up the alveolar walls and to alveolar capillaries. The function of PGP is unknown. TK- and CGRP-ir nerves in alveolar walls may be sensory and function as chemo-, stretch-, and/or immuno-receptors. TKs and CGRP released from alveolar fibers may influence the alveolar epithelium and the various non-epithelial alveolar cells, including immune cells. The alveolar TK and CGRP innervation may be of unrecognized importance in physiological and pathophysiological regulation of lung functions.
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PMID:Tachykinin-, calcitonin gene-related peptide-, and protein gene product 9.5-immunoreactive nerve fibers in alveolar walls of mammals. 184

This study describes the immunocytochemical distribution of five neuropeptides (calcitonin gene-related peptide [CGRP], enkephalin, galanin, somatostatin, and substance P), three neuronal markers (neurofilament triplet proteins, neuron-specific enolase [NSE], and protein gene product 9.5), and two synaptic-vesicle-associated proteins (synapsin I and synaptophysin) in the spinal cord and dorsal root ganglia of adult and newborn dogs. CGRP and substance P were the only peptides detectable at birth in the spinal cord; they were present within a small number of immunoreactive fibers concentrated in laminae I-II. CGRP immunoreactivity was also observed in motoneurons and in dorsal root ganglion cells. In adult animals, all peptides under study were localized to varicose fibers forming rich plexuses within laminae I-III and, to a lesser extent, lamina X and the intermediolateral cell columns. Some dorsal root ganglion neurons were CGRP- and/or substance P-immunoreactive. The other antigens were present in the spinal cord and dorsal root ganglia of both adult and newborn animals, with the exception of NSE, which, at birth, was not detectable in spinal cord neurons. Moreover, synapsin I/synaptophysin immunoreactivity, at birth, was restricted to laminae I-II, while in adult dogs, immunostaining was observed in terminal-like elements throughout the spinal neuropil. These results suggest that in the dog spinal cord and dorsal root ganglia, peptide-containing pathways complete their development during postnatal life, together with the full expression of NSE and synapsin I/synaptophysin immunoreactivities. In adulthood, peptide distribution is similar to that described in other mammals, although a relative absence of immunoreactive cell bodies was observed in the spinal cord.
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PMID:Distribution of five peptides, three general neuroendocrine markers, and two synaptic-vesicle-associated proteins in the spinal cord and dorsal root ganglia of the adult and newborn dog: an immunocytochemical study. 186 58

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
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PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36

Non-cholinergic, non-adrenergic vasodilation has been studied by transmural field stimulation of the isolated rat hepatic artery and compared with responses in the splenic artery. In the hepatic artery with rubbed endothelium, transmural stimulation caused a contracture that was blocked by phentolamine and potentiated after capsaicin. After pretreatment with guanethidine in order to deplete the neuronal stores of noradrenaline, the methoxamine-contracted hepatic artery was significantly relaxed by transmural stimulation; more efficiently than the splenic artery. This relaxation of the hepatic artery was attenuated following a 30 min exposure to capsaicin and largely blocked by tetrodotoxin (TTX). The relaxation by exogenous CGRP was independent of a functional endothelium. In contrast, vasodilation by substance P (SP) and neurokinin A (NKA), was completely dependent on an intact endothelium. Exogenous CGRP caused a near-complete relaxation of the methoxamine-contracted hepatic artery both before and after capsaicin treatment. CGRP was a more efficient relaxant of the hepatic than the splenic artery. These findings show that responses to transmural stimulation of the hepatic artery are modulated after pretreatment with capsaicin, indicating release of relaxing substances such as CGRP, presumably from capsaicin-sensitive neuronal stores. In conclusion, CGRP is a likely mediator of neuronal vasodilation in the rat liver, independent of the state of the endothelium.
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PMID:Vasodilation by calcitonin gene-related peptide (CGRP) and by transmural stimulation of the methoxamine-contracted rat hepatic artery after pretreatment with guanethidine. 194 24

Tachykinins and CGRP label two distinct populations of neurons innervating the digestive system: intrinsic and extrinsic, afferents. The bulk of SP/tachykinin innervation originates from intrinsic neurons, even though a minor component of this innervation derives from afferent neurons, which are mostly located in dorsal root ganglia. Afferent SP/tachykinin fibers are mainly confined to a perivascular location and to the submocosa in the gut, but are distributed also to the hepatobiliary pathway and pancreas. On the contrary, the extrinsic CGRP-containing afferents form a major component of the sensory innervation of the alimentary tract, including the rich CGRP innervation of the esophagus, stomach, hepatobiliary tract, pancreas, and vasculature, as well as a portion of non-vascular fibers distributed to the intestinal wall. Tachykinin and CGRP immunoreactivities appear to be colocalized in a population of nerve fibers, which are likely to be extrinsic, afferent, since colocalization of these peptide immunoreactivities has not been reported in intrinsic neurons. The presence of SP/NKA-encoding transcripts in the enteric nervous system and sensory ganglia and the lack of hybridization signal with RNA probes complementary to NKB mRNA indicate that the PPT I gene, but not the PPT II gene, is transcribed in these structures. This observation, along with receptor binding sites and radioimmunoassay data, which have failed to detect NKB receptor binding sites or immunoreactivity (Eysselein et al., 1990; Maggio, 1988; Mantyh et al., 1988; 1989) in the intestine of several mammals, is consistent with a differential expression of the two PPT genes in the periphery and in the central nervous system (Brecha et al., 1989; Warden and Young, 1988). A differential expression of the tachykinin-encoding genes, the existence of multiple tachykinin receptor subtypes (Mantyh et al., 1988; 1989), and the findings that tachykinins can be differentiated on the basis of the potency of their activities (Galligan et al., 1987; Maggio, 1988), support the possibility that each tachykinin is expressed in separate, and perhaps functionally distinct neuronal systems. alpha- and beta-CGRP genes also are differentially expressed according to the neuronal populations: alpha-CGRP mRNA is the most prominent form in sensory ganglia, and beta-CGRP mRNA is the only form detected in enteric neurons (Mulderry et al., 1988; Sternini and Anderson, 1990). In addition, distinct distributions of mRNAs generated from the two CGRP genes have been reported in the central nervous system (Amara et al., 1985). The differential expression patterns of alpha- and beta-CGRP mRNAs are consistent with a differential regulation of the alpha- and beta-CGRP genes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tachykinin and calcitonin gene-related peptide immunoreactivities and mRNAs in the mammalian enteric nervous system and sensory ganglia. 195 Jul 91

The present findings have revealed a new aspect of how mechanisms of gastric mucosal resistance to injury are called into effect and are coordinated by the nervous system. Capsaicin-sensitive sensory neurons in the stomach play a physiological role in monitoring acid influx into the superficial mucosa. Once activated, they strengthen gastric mucosal defense against deep injury, with a key process in this respect being an increase in blood flow through the gastric mucosa. This concept opens up completely new perspectives in the physiology and pathophysiology of the gastric mucosa if we consider that the long-term integrity of the gastric mucosa may be under the subtle control of acid-sensitive sensory neurons and that, vice versa, improper functioning of these neutral control mechanisms may predispose to gastric ulcer disease. The present observations also indicate that some of the peptides contained in gastric sensory nerve endings might fulfill a transmitter or mediator role in controlling gastric mucosal blood flow and integrity. Whereas substance P and neurokinin A are unlikely to play a role in the regulation of gastric mucosal blood flow, there is severalfold evidence that CGRP is very important in this respect. This peptide, which in the rat gastric mucosa originates exclusively from spinal sensory neurons, is released upon stimulation of sensory nerve endings and is extremely potent in facilitating gastric mucosal blood flow and in protecting the mucosa from injurious factors. Selective ablation of spinal sensory neurons containing CGRP weakens the resistance of the gastric mucosa against acid injury, which is most likely due to inhibition of protective vasodilator reflexes. We now aim at providing direct pharmacological evidence that antagonism of endogenously released CGRP results in similar pathophysiological consequences as ablation of capsaicin-sensitive sensory neurons.
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PMID:Role of peptidergic sensory neurons in gastric mucosal blood flow and protection. 195 29

Calcitonin gene-related peptide has been demonstrated in urinary bladder nerves, and suggested to play a role in local control of bladder motility. In isolated strips of pig detrusor muscle, calcitonin gene-related peptide did not affect spontaneous contractile activity, or contractions induced by high K+, carbachol, substance P, and electrical field stimulation. In contrast, calcitonin gene-related peptide elicited a concentration-dependent and pronounced (78-99%) relaxation of vesical arteries precontracted with endothelin-1, noradrenaline or prostaglandin F2 alpha. As a vasodilator, CGRP was approximately 50 times more potent than acetylcholine. Removal of the endothelium abolished acetylcholine-induced relaxation, but did not affect the relaxation produced by calcitonin gene-related peptide. Pretreatment with methylene blue, glibenclamide or indomethacin had no influence on CGRP's ability to relax the vessels. The inhibitor of NO-synthesis, NG-nitro-L-arginine, had no effect on the maximum vascular relaxation induced by calcitonin gene-relate peptide. It is concluded that in the pig, calcitonin gene-related peptide has no functionally important mechanical effects on isolated detrusor muscle strips, but is a potent dilator of vesical arteries. The vascular effects of the peptide are endothelium-independent, and seem to be exerted directly on the vascular smooth muscle.
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PMID:Difference in the actions of calcitonin gene-related peptide on pig detrusor and vesical arterial smooth muscle. 195 6

Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not displayed by the parental neuroblastoma. These properties include an inward (depolarizing) current with a conductance increase in response to activation of a bradykinin receptor, an inward (depolarizing) current with a conductance increase in response to the sensory excitotoxin capsaicin, the expression of sensory neuropeptides (substance P, CGRP and somatostatin), the expression of phosphatidylinositol-anchored molecules including adhesion molecules of the immunoglobulin superfamily that can be regulated in serum-free culture by nerve growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex virus infection. These lines thus provide appropriate models for the study of mechanisms involved in nociceptor activation and the regulation of expression of sensory-neuron specific markers including neuropeptides.
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PMID:Novel cell lines display properties of nociceptive sensory neurons. 197 43

Capsaicin has been used extensively as an experimental tool and in traditional and proprietary topical medications for acute soft tissue injuries. More recently it has been prescribed for several chronic pain conditions where it is usually administered topically for periods of several weeks. Here we have studied the consequences of this mode of application in the rat. Capsaicin cream (0.075% or 0.75%), or a vehicle cream, was applied twice daily to the hind paws of rats for a continuous period of 10 weeks. The hind paws treated with 0.75% capsaicin (but not 0.075%) because transiently hyperalgesic, but there were no signs of discomfort or distress associated with the treatment. After 10 weeks of capsaicin application, the ability of C fibres to produce neurogenic extravasation was markedly reduced. After 4 weeks of recovery this ability returned to normal in 0.075% capsaicin-treated animals, but remained impaired in the 0.75% group. This latter group showed a partial recovery 12 weeks after the end of treatment. The levels of substance P and CGRP in the sural nerve supplying the treated skin area were unchanged after both the 0.075% and 0.75% capsaicin treatments. The results suggest that the topical application of capsaicin at low concentration produces a reversible impairment of the terminals of C fibres in the skin without greatly exciting those fibres and without affecting the properties of cell soma. The number of afferent neurones in the L5 dorsal root ganglion projecting through the sural nerve was unchanged after 0.75% capsaicin treatment, suggesting that the topical capsaicin treatment does not produce any cell death in the adult animal.
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PMID:The consequences of long-term topical capsaicin application in the rat. 205

The effect of peptidase inhibitors on neuropeptide release from peripheral endings of capsaicin-sensitive sensory neurons was studied in cerebral superior sagittal and transverse sinuses of guinea-pig. Capsaicin (1 microM)-evoked release of substance P-like immunoreactivity (SP-LI) was increased in a concentration-dependent manner by thiorphan (0.1-10 microM). Captopril (10 microM) or a mixture of bestatin (10 microM), leupeptin (10 microM) and bacitracin (10 microM) did not affect the capsaicin-evoked SP-LI release. Thiorphan (10 microM) increased also the capsaicin-evoked release of neurokinin A-like immunoreactivity (TK-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) by 228% and 172%, respectively, while captopril (10 microM) was without effect. Thiorphan (10 microM), but not captopril (10 microM), enhanced by 239% CGRP-LI release induced by bradykinin (10 microM). In the cerebral venous vessels neutral endopeptidase (EC 3.4.24.11, NEP)-like activity was 58.8 +/- 6.1 pmol/mg protein/min, while angiotensin converting enzyme-like activity was below the detection limit of the assay. A thiorphan-sensitive mechanism, putatively attributable to NEP, plays a major role in the inactivation of peptides released from or acting on capsaicin-sensitive sensory fibres of cerebral venous sinuses of guinea-pig.
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PMID:The effect of thiorphan on release of sensory neuropeptides from guinea-pig cerebral venous sinuses. 206 52


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