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)

Immunohistochemical studies on rats showed cysteamine to deplete immunoreactive somatostatin, but not substance P, in the substantia gelatinosa of the spinal trigeminal nucleus and spinal cord. The effect of cysteamine treatment on chemical pain was investigated using capsaicin as the pain-producing stimulus. Thermal pain was assessed with a hot plate test after cysteamine treatment. It was found that cysteamine did not alter the hind paw lick latency in the hot plate test or the number of forepaw wipes after application of a drop of capsaicin into the cornea, compared to normal animals. In capsaicin-treated animals a significantly lower number of forepaw wipes were seen after corneal capsaicin application. However, in cysteamine-treated animals slower wiping was observed compared to untreated and capsaicin-treated animals. This suggests that somatostatin may be of importance for the modulation of nociceptive information, although it is not a major pain transmitter.
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PMID:Effects of cysteamine on pain behaviour and on somatostatin- and substance P-like immunoreactivity in the substantia gelatinosa of the rat. 620 49

Neonatal injection of 6-hydroxydopamine (420 mg/kg s.c.) lowered thermal nociceptive threshold (hot plate and tail immersion tests) and increased levels of substance P-like immunoreactivity in the skin (paws, tail, area of vibrissae) of Wistar rats. Chemical ablation of primary afferents, induced in either neonatal or adult rats by systemic administration of capsaicin, increased thermal nociceptive threshold (hot plate), irrespective of 6-hydroxydopamine pretreatment, and reduced substance P-like immunoreactivity in the hind-paw skin of either control or sympathectomized rats. Capsaicin pretreatment of neonatal but not adult rats produced antinociceptive effect in the tail-immersion test and completely reversed the hyperalgesic effect of sympathectomy, without affecting levels of substance P-like immunoreactivity in the tail skin. These findings indicate that sympathetic nerves and different subsets of capsaicin-sensitive primary afferents are involved in the processing of thermal nociceptive input. Corneal and cutaneous lesions were induced by neonatal sensory denervation with capsaicin. Sympathectomy afforded protection against the development of corneal pathology, while it did not affect the occurrence of cutaneous lesions. It appears that a balance in the neuronal activity between sympathetic neurons and trigeminal sensory neurons is critical for maintaining the normal trophism of the cornea, and that sensory neuropeptides play a key role in the maintenance of normal trophism of the skin.
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PMID:Relative contribution of sympathetic and sensory nerves to thermal nociception and tissue trophism in rats. 750 78

We evaluated the effects of nitric oxide (NO) generators and endogenous production of NO elicited by substance P (SP) in the angiogenesis process. Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring the growth and migration of endothelial cells isolated from coronary postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]-SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP). Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine incorporation and in total cell number. Exposure of the cells to NO generating drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a dose-dependent increase in endothelial cell migration. Capillary endothelial cell proliferation and migration produced by SP were abolished by pretreatment with the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro-L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium-dependent NO synthase. Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis.
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PMID:Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. 752 53

Inoculation of the scarified cornea with herpes simplex virus (type 1) leads to herpetic infection of trigeminal ganglion cells. A recent study of the susceptibility of ganglion cells revealed that there may be at least four populations of trigeminal ganglion cells that are infectable by herpes. Two classes were identified by their neuropeptide content: Substance P or calcitonin gene-related peptide. One class was identified by its affinity for a monoclonal antibody, SSEA-3. The fourth class was recognized by its common affinity for both the monoclonal antibody LD2 and for the lectin Bandeiraea simplicifolia isolectin. However, there has been no direct evidence of which types are infected directly as a result of retrograde transport from the corneal site and which may be infected by cell-to-cell spread. The aim of this study was to determine which classes of neurons, which are known to become infected with HSV after ocular inoculation, supply corneal innervation. We have identified four classes of trigeminal ganglion neurons that supply axons to the central cornea of the mouse, on the basis of their ability to transport Fluoro-Gold retrograde from axons in the central corneal epithelium and stroma. About 40% of the neurons that innervate the cornea contain Substance P or calcitonin gene-related peptide; about 60% of the neurons that innervate the cornea react with the monoclonal antibody SSEA-3. About 36% of all neurons in the whole ophthalmic division react with the LD2 or Bandeiraea simplicifolia isolectin, and Fluoro-Gold labels only 2% of them.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical identification of trigeminal ganglion neurons that innervate the mouse cornea: relevance to intercellular spread of herpes simplex virus. 767 19

The distribution of substance P (SP) within the nerve fibers of the rat cornea and iris was studied using electron microscopic immunohistochemistry. Numerous SP-immunoreactive fibers were found throughout the corneal and iridal stroma. The most intense staining was found within varicosities containing numerous vesicles. Similar SP-immunoreactive varicosities were found in fibers in close proximity to the iris sphincter and dilator muscles. On account of previous ultrastructural work the SP-containing fibers and varicosities must be assumed to be of trigeminal origin. Additionally, the distribution of SP and calcitonin gene-related peptide (CGRP) in corneal and iridal fibers of rats is similar, suggesting that CGRP and SP are colocalized and may be coreleased from the same varicosities.
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PMID:Substance P in rat corneal and iridal nerves: an ultrastructural immunohistochemical study. 768 59

The tachykinin-1 gene in mammals produces structurally-related regulatory peptides, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide-gamma. The production of these peptides is regulated by both differential mRNA transcription and post-translational precursor processing. Such processes are known to be highly tissue- and species-specific. In this study, we have examined tachykinin-1 gene expression and precursor processing in porcine ocular tissues by employing specific tachykinin radioimmunoassays coupled with reverse phase HPLC characterization. Optic nerve, cornea, iris, ciliary body, retina, choroid and sclera were micro-dissected from freshly enucleated porcine eyes (n = 10). Following acidified ethanol extraction of tissues, dried extracts were reconstituted and subjected to two radioimmunoassays, one of which is highly specific for intact SP, the other for NKA, NKB, NPK and neuropeptide-gamma. In all tissue extracts except the retina, the molar concentration of SP immunoreactivity was significantly greater than that of NKA. These data would imply expression of both alpha- and beta-preprotachykinin-1 in these ocular tissues. Reverse phase HPLC analysis confirmed the presence of authentic SP and NKA in all tissue extracts. However, in extracts of the retina, NKA immunoreactivity co-eluted with synthetic NPK standard. These chromatographic data suggest differential processing of the beta-preprotachykinin-1 precursor in the retina compared with the other ocular tissues. Thus differential mRNA transcription of the tachykinin-1 gene coupled with differential precursor processing appears to occur in porcine ocular tissues and may be a process of functional significance in the regulation of visual physiology.
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PMID:Tachykinin-1 gene products in porcine ocular tissues: evidence for transcriptional and post-translational regulation. 768 18

The neuropeptide substance P (SP) was found to stimulate DNA synthesis and cell growth for epithelial cells (cornea and lens) in a serum-free environment. The length of treatment time was shown to be important since longer times shifted the dose-response curve to the left. In short-term DNA synthesis studies (40 h) the stimulation with SP (or synergism with insulin) was not apparent until close to 10 microM, however, when DNA synthesis assays were carried out over a long period of time (5 days) stimulation with SP was seen at 1 pM. The stimulation of DNA synthesis by SP was synergistic with insulin for lens epithelial cells, but little synergism was seen with corneal epithelial cells. It cell growth studies on lens epithelial cells SP also showed growth stimulation by itself and synergism with insulin at concentrations of 1-2 pM. The neuropeptide calcitonin gene related peptide (CGRP) showed no DNA synthesis stimulating ability on epithelial cells by itself at concentrations as high as 2.5 microM; however, it was synergistic with SP at a concentration of 0.025 microM. SP pretreatment of epithelial cells for 2 h causes an increase in cellular sensitivity to subsequent addition of either SP or insulin. This increase is consistent with the hypothesis that either the signal from SP persists after its removal from the cell or the dissociation time for SP from its receptor is longer than the wash time.
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PMID:Stimulation of epithelial cell growth by the neuropeptide substance P. 769 29

Trigeminal primary neuronal cell bodies were labeled by retrograde transport of Fluoro-gold (FG) from the nasal mucosa of rats. The trigeminal ganglion containing the labeled cell bodies were processed for double stain for calretinin- and tachykinin-immunoreactivities (CR- and TK-irs). Except for a few contralateral cells, all the cells that innervated the nasal mucosa (NM cells) were confined to the ophthalmo-maxillary division of the trigeminal ganglion ipsilateral to the FG application. In the dorsal two-thirds of the ganglion, NM cells formed a cluster in the rostromedial part of ophthalmo-maxillary division (the rostromedial cluster). In the ventral third, the number of cells in the rostromedial cluster markedly decreased. Instead, numerous NM cells were found in the caudolateral part of the ophthalmo-maxillary division (the caudoventrolateral cluster). CR- and TK-irs were detected in 18% and 54% of overall population of NM cells, respectively. Virtually all of CR-immunoreactive (-ir) NM cells coexpressed TK. Although the proportion of TK-ir cells, irrespective of CR-ir, was similar for both clusters, CR-ir cells were more frequent in the caudoventrolateral cluster than in the rostromedial cluster. In the dorsal 1/3 of the ganglion where all the NM cells belonged to the rostromedial cluster, only 8.4% exhibited CR-ir. On the other hand, as much as 30.1% of NM cells expressed CR-ir in the ventral 1/3 where most NM cells were found in the caudoventrolateral cluster. Trigeminal cell bodies innervating the cornea and conjunctivum were located in the rostromedial part of the ophthalmo-maxillary division.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calretinin-immunoreactivity in trigeminal neurons innervating the nasal mucosa of the rat. 811 27

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
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PMID:Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. 863 27

Stimulation of the cornea activates neurons in two distinct regions of the spinal trigeminal nucleus: at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis and at the transition between trigeminal subnucleus caudalis and the upper cervical spinal cord as estimated by expression of the immediate early gene, c-fos. To determine if receptors for substance P or neurokinin A, neurokinin 1 and neurokinin 2 receptors, respectively, contribute to the production of Fos-positive neurons in these brainstem regions, receptor-selective antagonists were given intracerebroventricularly 15 min prior to stimulation of the cornea in anesthetized rats. The number of Fos-positive neurons produced in superficial laminae at the trigeminal subnucleus caudalis/cervical cord transition by application of the selective small fiber excitant, mustard oil, to the corneal surface was reduced by the neurokinin 1 receptor antagonist, CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). Combined pretreatment with CP99,994 and the competitive N-methyl-D-aspartate receptor antagonist, CPP, caused a greater reduction in c-fos expression at the subnucleus caudalis/cervical cord transition than after either drug alone suggesting interaction between receptors for glutamate and substance P. Tachykinin receptor antagonists did not reduce the number of Fos-positive neurons produced at the subnucleus interpolaris/subnucleus caudalis transition. The elevation in plasma concentration of adrenocorticotropin, but not the increases in arterial pressure or heart rate, evoked by corneal stimulation was prevented by pretreatment with CP99,994 or MEN10,376 at doses lower than those needed to reduce c-fos expression. The results indicate that receptors for substance P and neurokinin A contribute to the transmission of sensory input from corneal nociceptors to brainstem neurons in trigeminal subnucleus caudalis and to increased activity of the hypothalamo-pituitary axis that accompanies acute stimulation of the cornea.
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PMID:Selective blockade of substance P or neurokinin A receptors reduces the expression of c-fos in trigeminal subnucleus caudalis after corneal stimulation in the rat. 946 Jul 60


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