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)

Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.
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PMID:Acute effect of substance P in immunologic vasculitis in the rat colon. 172 22

By use of two antisera (alpha-CRFA, alpha-CRFB) raised against conjugates of o-CRF and bovine thyroglobulin, cryostat sections of formaldehyde-fixed gelatin models containing o-CRF can be stained. The staining intensity was quantitated by use of an automated microfluorimeter and was shown to be dependent on the concentration of o-CRF (1-300 microM) added to the gel. Determination of the CRF staining intensity after incorporation of o-CRF-related peptides and fragments indicated that both antisera reacted with the C-terminal region of o-CRF. They showed poor cross reactivity with r-CRF fixed in the gel. In the same models, r-CRF could be immunostained efficiently by use of an antiserum (alpha-CRFC) raised to a conjugate of r-CRF and thyroglobulin. This antiserum reacted with the N-terminal and midportion parts but not with the C-terminal fragment of o-CRF fixed in the gels. By use of both o-CRF antisera nerve fibers can be stained in the rat hypothalamus (median eminence) and in the medulla oblongata (spinal trigeminal tract and nucleus) and spinal cord (dorsal horn). Immunoinhibition experiments showed that o-CRF caused a concentration-dependent quenching (0.001-1 microM) of the immunostaining of o-CRF-containing models, rat median eminence and medulla oblongata preparations. alpha-CRFC also stained CRF immunoreactive (CRFi) fibers in the rat hypothalamus with an equal distribution to that found with the o-CRF antisera. However, no immunostaining was found in the spinal trigeminal nucleus and tract and in the dorsal horn, indicating that these fibers store different CRF-related products from those found in the hypothalamus. The CRFi in the medulla oblongata and spinal cord induced by alpha-CRFA was completely abolished 1 week after treatment of adult rats with capsaicin, a substance known to deplete Substance P (SP) from those areas. Gels incorporated with SP showed a concentration-dependent increase (range 10-1000 microM) in immunostaining with both o-CRF sera but not with the r-CRF antiserum. In addition, incubation of o-CRF sera with SP caused a concentration-dependent quenching (range 10-100 microM) of immunostaining in SP-containing models. SP at a concentration of 100 microM was also effective in quenching the CRFi in the dorsal horn and spinal trigeminal area. Quenching was also obtained with the C-terminal part of o-CRF (range 0.002-0.1 microM), which indicates that both CRF antisera contain an immunoglobulin which recognizes determinants on CRF as well as on SP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Corticotropin-releasing factor immunostaining in the rat spinal cord and medulla oblongata: an unexpected form of cross-reactivity with substance P. 243 2

Characteristics of in situ substance P release from the lumbar dorsal horn were investigated in decerebrated rabbits. Noxious mechanical stimuli produced by pinching the skin of a hind leg ipsilateral to the perfusion site remarkably and significantly increased the release of immunoreactive substance P, which was identified as substance P itself, using separation with high-performance liquid chromatography and radioimmunoassay. The noxious pinch did not affect the release of immunoreactive substance P, when applied to the contralateral hind leg. Both the basal and pinch-evoked release of immunoreactive substance P were largest in the dorsolateral part of the dorsal horn. The pinch-evoked release of immunoreactive substance P was abolished when the dorsal horn was perfused with a Ca2+-free medium containing 7 mM Mg2+ or with a medium with 10 microM tetrodotoxin added. The evoked release of immunoreactive substance P was also abolished following pretreatment of a stimulated region with the local anesthetic dibucaine, a procedure which inhibited the pinch-evoked aversive behavior in freely-moving rabbits. Among a variety of natural stimuli applied to the hind leg, noxious pinch and a subcutaneous injection of formaldehyde solution significantly evoked the release of immunoreactive substance P from the dorsal horn. The most intense heat or scalding stimulation increased the immunoreactive substance P release in two out of five experiments. However, other natural stimuli such as ice-cold, warm, noxious heat and innocuous mechanical stimuli produced no apparent changes in the release of immunoreactive substance P. These results suggest that among the noxious stimuli, only mechanical and inflammatory but not thermal stimuli lead to a release of substance P from the primary afferent terminals in the dorsal horn. The present findings suggest that, at least in rabbits, substance P-containing primary afferents have high-threshold mechanoreceptors. Substance P may participate in the transmission of information related to noxious mechanical and inflammatory stimulation from the periphery to the dorsal horn.
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PMID:Stimulus specificity of peripherally evoked substance P release from the rabbit dorsal horn in situ. 247 12

The taste buds and associated nerves in the guinea pig, rat, cat, and mouse were investigated by immunocytochemistry and formaldehyde-induced fluorescence histochemistry. The antisera used were against spot 35 protein, neuron-specific enolase (NSE), neurofilament protein (NFP), and substance P. The spot 35 protein immunoreactivity was confined to taste bud cells in the guinea pig and rat; the immunoreactive cells, slender in shape, comprised half the number of the total taste bud cells in the guinea pig but were fewer in the rat. For NSE, on the other hand, taste bud cells as well as neural elements localized in both the taste bud and the subepithelial connective tissue were immunoreactive in all the species investigated. Furthermore, all of the spot 35 protein-immunoreactive cells proved to be NSE-immunoreactive in the guinea pig and rat. For NFP, neither the bud cells nor the nerves in the taste bud were reactive, whereas a part of nerves in the connective tissue was immunostained in all the species. The antiserum against substance P exclusively detected some parts of nerves in and out of the taste buds in the cat, rat, and mouse. The aminergic innervation was rather meager and appeared in the nerve fibers localized in the taste buds and connective tissue of the cat and mouse.
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PMID:Immunocytochemistry of neuron-specific proteins and neuropeptides in taste buds and associated nerves. 247 4

Selective retrograde labelling with [3H]serotonin ([3H]5-HT) can be used to identify serotonergic cell bodies after specific [3H]5-HT uptake by the corresponding nerve terminals. In the present study, we demonstrate that autoradiography of this [3H]5-HT radiolabelling can be combined with immunocytochemical detection of endogenous serotonin, GABA or substance P on the same tissue section. The midbrain raphe serotonergic projections to the olfactory bulb and the spinal projections of medullary serotonergic nuclei were investigated. The specificity of retrograde labelling with [3H]5-HT was confirmed by immunoreactivity of the radiolabelled cells for serotonin, using an antiserum specific for formaldehyde-fixed serotonin. After spinal injections of [3H]5-HT, many retrogradely labelled cells in the medullary raphe were immunopositive for substance P, and a few for GABA. These results are in agreement with the available information on the co-existence of putative transmitters in the spinal projections of caudal raphe neurons. Therefore, autoradiography of [3H]5-HT retrograde labelling combined with immunocytochemistry offers a possibility to test the specificity of transmitter-selective retrograde labelling, to identify transmitter-defined neuronal interactions and to investigate the projection fields of multitransmitter containing neurons.
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PMID:Tracing specific transmitter pathways in the rat CNS: combination of [3H]serotonin retrograde labelling with immunocytochemical detection of endogenous transmitters. 248 94

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.
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PMID:Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response. 290 80

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.
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PMID:[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system]. 372 60

Noxious stimulus-induced changes in substance P (SP) release in the dorsal horn of the spinal cord and met-enkephalin release in the brain stem were investigated. For this purpose, a specially devised push-pull cannula system was used. Noxious stimuli were applied to the skin of the hind paw of rabbits and the lumbar dorsal horn was perfused using a push-pull cannula. Substance P concentration in the perfusate was assayed by radioimmunoassay. Noxious mechanical stimuli, but not thermal stimuli, increased the release of immunoreactive substance P (iSP). Innocuous stimuli did not affect the release of these peptides. Systemic administration of an analgesic dose of morphine (1 mg/kg) did not inhibit the iSP release induced by noxious stimuli. This suggests that morphine analgesia may not be mediated by a blocking action on SP release from the primary afferent terminals at the dorsal horn. The nucleus reticularis gigantocellularis (NRGC) of rat medulla oblongata was perfused in situ and the effects of noxious stimuli on the release of immunoreactive met-enkephalin were examined. Formalin and thermal stimuli, but not mechanical stimuli, increased the "tonic" release of immunoreactive met-enkephalin from NRGC. No "phasic" increase was observed following the three forms of stimulation. Topical application of dibucaine abolished the formalin-induced increase in the release of met-enkephalin. Therefore, the possibility that persistent noxious stimuli may activate the met-enkephalin-containing fibers in the NRGC must be given consideration.
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PMID:Experimental pain and neuropeptides. 608 33

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng . min-1 . kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p less than 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.
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PMID:Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system. 618 93

Substance P (SP)-immunoreactive nerve fibres were searched for at all levels of both fetal and adult human lower respiratory tract. Because the demonstrability of substance P immunoreactivity varies between different animal species, rabbit pulmonary tissue was also subjected to SP immunohistochemistry. Human irises and corneas served as positive human controls. The specimens were taken from 10 human lungs during pulmonary operations. Tracheal tissue was obtained from three patients during bronchoscopy. Five fetal human lungs were examined. Human specimens examined included the trachea, main bronchi, segmental bronchi, and peripheral pulmonary tissue. In addition, the tracheobronchial tissues of four rabbits were studied. SP immunoreaction was demonstrated in formaldehyde-fixed cryostat sections by either the indirect immunofluorescence technique or the peroxidase-antiperoxidase procedure. Both monoclonal and conventional antibodies to SP were tested. In the rabbit SP-immunoreactive nerves were found in both the submucosa and the smooth muscle layer of the main bronchi and trachea. Specimens from human trachea, bronchi, and bronchioli were all negative. Since the SP immunoreaction was easily demonstrated in both human cornea and human iris, it was concluded that there are no SP-immunoreactive nerves in the human pulmonary tissues or that their SP content is very low and below the sensitivity of all the techniques used.
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PMID:Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man. 619 99


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