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 whether the depletion of neuropeptides from sensory nerve terminals induced by capsaicin modifies the healing rate of experimental corneal wounds in adult rabbits. Capsaicin (33 or 3.3 mM solutions) was administered topically and/or by a single retrobulbar injection to one eye while the fellow eye, treated with the vehicle, served as a control. After 1-3 weeks of treatment, an epithelial wound was made in the center of the cornea of both eyes with n-heptanol. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. Combined treatment with 33 mM retrobulbar and 3.3 mM topical capsaicin for 3 weeks induced a significant delay in epithelial migration rates and in wound closure times (P less than 0.05). Topical or retrobulbar capsaicin alone for 3 weeks and combined treatment lasting only 1 week were not sufficient to modify wound healing times. The substance P antagonist, spantide (3 mM), applied topically for 1-3 weeks before or immediately after corneal wounding was also ineffective in changing wound closure rates. These findings suggest that the delayed wound healing observed after prolonged treatment with capsaicin could be due to a sustained depletion of neuropeptides from corneal sensory endings, supporting the hypothesis that trophic effects of sensory nerves on corneal epithelium are, at least in part, mediated by neuropeptides contained in peripheral nerve terminals.
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PMID:Effects of capsaicin on corneal wound healing. 169 37

We have investigated the possible effect of substance P (SP), a main mediator of neurogenic inflammation, on the growth of capillary vessels in vivo, and on the proliferation of cultured endothelial cells in vitro. Slow release preparations of SP were implanted into the avascular cornea of New Zealand White rabbits and vessel growth was monitored daily through a slit lamp stereomicroscope. SP (1-5 micrograms/pellet) induced a marked neovascularization. A selective NK-1 receptor agonist [beta-Ala4, Sar9, Met(O2)11]-SP(4-11) also induced neovascularization. The addition of SP to serum-free cultured endothelial cells, isolated from bovine adrenals (BACE) and from human umbilical cord veins (HUVE), increased proliferation of both cell lines in a concentration-dependent manner with maximal activity at 10(-8) M (BACE) and 10(-10) M (HUVE). The selective NK-1 receptor agonist induced a similar proliferative action on both cell lines, while the selective NK-2 receptor agonist [beta-Ala8]-NKA(4-10) and the selective NK-3 receptor agonist [MePhe7]-NKB had no significant effect. Two different SP antagonists [D-Pro2, D-Trp7,9]-SP and [D-Pro4, D-Trp7,9,Phe11]-SP (4-11) blocked the response to SP. These findings indicate that SP can directly stimulate the process of neovascularization, probably through induction of endothelial cell proliferation. This hitherto unraveled activity of SP could play a key role in the trophic action produced by activation of the efferent function of peripheral endings of primary sensory neurons.
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PMID:Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. 170 Dec 6

The peripheral territories of sheep trigeminal neurons which send their central process to the brainstem through the oculomotor nerve were investigated by the use of fluorescent tracers in double-labeling experiments. For this purpose Diamidino yellow (DY) injection into the oculomotor nerve was combined with Fast blue (FB) injection either into the extraocular muscles (EOMs), or the cornea, or the superior eyelid. Double-labeled DY + FB cells were found in the ophthalmic region of the trigeminal ganglion in addition to single-labeled DY or FB cells. The DY and DY + FB-labeled trigeminal cells were analysed immunocytochemically for their content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and cholecystokinin-8 (CCK-8)-like. All single-labeled DY cells showed SP-, CGRP- or CCK-8-like immunoreactivity. Double-labeled DY + FB neurons innervating the EOMs were immunoreactive for each of the three peptides, whereas double-labeled neurons supplying the cornea were only CGRP-like positive. The findings suggest that, in the sheep, trigeminal neurons which send their process centrally through the oculomotor nerve supply the EOMs, the cornea, and the superior eyelid and contain neuropeptides which are usually associated with pain sensation.
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PMID:Peripheral territory and neuropeptides of the trigeminal ganglion neurons centrally projecting through the oculomotor nerve demonstrated by fluorescent retrograde double-labeling combined with immunocytochemistry. 171 31

Substance P, a putative neurotransmitter peptide present in a subpopulation of small sensory neurons, was measured in the walls of feline cranial arteries and systemic veins and arteries using a sensitive and specific radioimmunoassay. Substance P immunoreactivity exhibited a retention time identical to that of synthetic substance P when vessel extracts were subjected to reverse phase high performance liquid chromatography. Levels in cephalic arteries (453-1083 fmol/mg protein) were at least twice as high as amounts in systemic arteries and veins, and were significantly higher than those measured in the cornea and lip. Unilateral excision of the trigeminal ganglion decreased the peptide by 44 to 86 per cent in ipsilateral intracranial and extracranial arteries (e.g. external and internal maxillary, lingual, temporal, anterior, middle and posterior cerebral, superior cerebellar and posterior communicating arteries). Extracranial arteries were decreased on average by 78 per cent, whereas intracranial arteries were reduced by 55 per cent. Unilateral removal of the superior cervical sympathetic ganglion was without effect. The described pattern of sensory innervation provides a possible explanation for the referral of pain to the forehead and anterior scalp during attacks of migraine, and with arteritis and thrombosis involving vascular structures within the posterior fossa, the circle of Willis and the external carotid system of man.
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PMID:Substance P and the sensory innervation of intracranial and extracranial feline cephalic arteries. Implications for vascular pain mechanisms in man. 240

Using immunohistochemical methods, substance P is localized to nerves of the human eye. Immunoreactive nerve fibers occur in the cornea, about limbal blood vessels, and within the trabecular meshwork. Substance P-like immunoreactive nerve fibers surround uveal blood vessels, especially in the choroid and ciliary body. Immunoreactive nerves are seen in ciliary processes. The ciliary muscle is innervated, as are the iris dilator and sphincter muscles. Apposition of immunoreactive nerves to uveal melanocytes is apparent. The distribution of substance P-like immunoreactive nerves in the human eye parallels that found in other mammals. While substance P probably has important neurotransmitter or neuromodulator roles in the eye, further physiologic studies are required to define its ocular function.
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PMID:Substance P-like immunoreactive nerves in the human eye. 241 Dec 47

Substance P-like immunoreactivity (SPLI) is present in the pia mater, arachnoid and pial vessels (leptomeninges) of the rat. Unilateral electrolytic lesions of the trigeminal ganglion decreased levels of SPLI in leptomeninges on the lesioned side. Levels did not change following unilateral or bilateral superior cervical ganglionectomies or after i.c.v. injections of 6-hydroxydopamine, sufficient to deplete norepinephrine in pial arteries by more than 90%. SP levels did not decrease in leptomeninges or in blood vessels within the circle of Willis following treatment of adult or neonatal rats with capsaicin despite the fact that levels were reduced in the cornea and dorsal spinal cord in these same animals. These results suggest that not all substance P-containing sensory fibers are susceptible to the peptide-depleting effects of capsaicin.
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PMID:Substance P-like immunoreactivity in rat forebrain leptomeninges and cerebral vessels originates from the trigeminal but not sympathetic ganglia. 243 68

Using a double labeling indirect immunofluorescent technique, we studied the guinea pig trigeminal ganglion and eye for co-localization of substance P and calcitonin gene-related peptide. In the trigeminal ganglion, the number of neurons immunoreactive for calcitonin gene-related peptide significantly outnumber those immunoreactive for substance P, but virtually all substance P positive neurons are immunoreactive for calcitonin gene-related peptide. In the eye, a complex pattern of co-localization is present; both peptides co-localize in most immunoreactive nerve fibers. Nerve fibers immunoreactive only for calcitonin gene-related peptide tend to be concentrated in the cornea and posterior ciliary body. Nerve fibers immunoreactive only for substance P are present in relation to both iris muscles. Sensory denervation by intracranial transection of the ophthalmic and maxillary nerves fails to eliminate these substance P positive but CGRP negative iris nerve fibers. These findings indicate an alternative origin for substance P immunoreactive nerves supplying the iris muscles in this species.
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PMID:Distinct substance P and calcitonin gene-related peptide immunoreactive nerves in the guinea pig eye. 244 7

Within the avian cornea collagen type IV is preferentially and characteristically localized to the epithelial and endothelial basement membranes. In the present paper, we demonstrate that collagen type IV also is present within the corneal stroma coincident with the development and distribution of corneal nerves indicating that intra-stromal fibers are associated with Schwann cells or an equivalent cell type. We also demonstrate intra-stromal fibers of collagen type IV orthogonal to the epithelial basement membrane. These novel structures are most prominent on the tenth day of development and become progressively less distinct until they are no longer detectable on the eighteenth day of development. Substance P immunoreactivity is prominently expressed by nerves innervating the epithelium. The first substance P immunoreactive nerves are detected on the twelfth day of development, concomitant with the initiation of epithelial innervation and not the extension of nerves through the stroma. Such nerve fibers become more numerous with progressive development and demonstrate extensive association with both basal and superficial epithelial cells. Thus, the avian cornea is richly supplied with substance P primary afferents. The expression of substance P immunoreactivity correlates directly with the initiation of innervation of the corneal epithelium.
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PMID:Avian corneal nerves: co-distribution with collagen type IV and acquisition of substance P immunoreactivity. 244 29

A study was made of the distribution of Substance P-immunoreactive fibers in chick cornea and uvea in whole mount preparation, using the indirect immunofluorescence technique. The development of these fibers during embryogenesis was also investigated. SP-fibers were present in all chick eye structures, in the various prenatal and postnatal stages examined. Their distribution was comparable with that observed by other workers in mammals. Transformation of the iris musculature from smooth to striated, during development, is not accompanied by significant changes in SP-ergic innervation.
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PMID:Distribution and development of substance P immunoreactive axons in the chick cornea and uvea. 245 5

The immunologically detected neuropeptides methionine enkephalin (ME), substance P (SP), beta-endorphin (beta-End), and alpha-melanocyte stimulating hormone (alpha-MSH) were purified from bovine corneal extracts by gradient, followed by isocratic, reversed phase-high performance liquid chromatography (RP-HPLC) and characterized, after both chromatographic steps, by radioimmunoassay (RIA). Immunologically detected ME and SP were purified from canine corneal extracts by gradient RP-HPLC and characterized by RIA. An anatomical study of the bovine cornea separated the cornea into an epithelium-enriched and a stroma-enriched portion. After gradient RP-HPLC, RIA demonstrated that all the ME-like immunoreactivity was located in the corneal epithelium, whereas the SP-like immunoreactivity was distributed between the stroma and epithelium in an approximate two-to-one ratio.
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PMID:Purification, characterization, and localization of neuropeptides in the cornea. 247 68


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