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)

Dynorphin A(1-17), the proposed endogenous ligand for the kappa receptor, has been reported to demonstrate no antinociceptive activity when tested in analgesic assays involving noxious (heat (e.g., tail-flick and hot-plate assays). By using a rat tail-flick analgesic assay that utilizes extreme cold as its noxious stimulus (an ethylene glycol-water mixture maintained at -10 degrees C), we have recently reported a dose-related and naloxone-reversible antinociceptive effect for i.c.v. administered dynorphin A(1-17). To elucidate the biochemical mechanism of this antinociception, we designed a push-pull perfusion system which would allow us to measure changes in neuropeptide release in the spinal cord during exposure to noxious heat or cold. Male Sprague-Dawley rats were implanted surgically with two lengths of PE-10 tubing inserted into the spinal subarachnoid space via the cisterna magna, with the push cannula at the level of T-1, and the pull cannula at the rostral edge of the lumbar enlargement. At the time of testing, samples of cerebrospinal fluid were collected both in the presence and absence of a noxious stimulus. Substance P (SP) and somatostatin (SST) levels were measured by radioimmunoassay. Exposing the animal's tail to the noxious cold (30 sec/min for 20 min) resulted in a significant elevation in SP release (69% above base-line levels), but no change in the level of SST release. Conversely, exposure to noxious heat (50 degrees C, 20 sec/min for 20 min) produced a significant increase in SST release (56% above base line), but no change in the level of SP release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17). 169 Feb 93

A defective histaminergic dilating system in the digital vasculature has been proposed for the pathophysiology of Raynaud's phenomenon but this is not supported by studies of digital intradermal responses to histamine or agents which cause histamine release. The vascular responses (measured by planimetry and laser Doppler flowmetry) of digital skin over the middle phalanx to intradermal histamine, compound 48/80 and Substance P have now been studied at low temperatures (because it is in the cold that Raynaud's phenomenon occurs) in normal controls and patients with primary Raynaud's phenomenon. A cold-related attenuation of mast cell histamine release by compound 48/80 was observed in both normal and Raynaud's subjects. These results do not support a major histaminergic defect in the pathogenesis of Raynaud's phenomenon.
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PMID:Vascular responses to histamine at low temperatures in normal digital skin and Raynaud's phenomenon. 171 28

1. The effect of capsaicin pre-treatment on adrenal catecholamine (CA) secretion in response to stress is controversial. In earlier experiments performed under pentobarbitone anaesthesia, the release of CA in response to stress was complicated by the effects of the barbiturate anaesthesia. 2. In the present study we have used conscious freely moving rats with indwelling cannulae to study the effect of neonatal capsaicin pre-treatment on the plasma CA response to different types of stressors (swimming stress, hypovolaemic stress, immobilization stress and cold stress). 3. After swimming for 20 min, plasma noradrenaline (NA) levels increased by 8-fold and adrenaline by 2-fold in control rats. The increase in plasma NA levels in the capsaicin group was attenuated at 10 min of swimming compared with the vehicle group (P < 0.05). 4. With hypovolaemic stress, there were no differences in plasma CA levels, blood pressure and heart rate between the capsaicin group and the vehicle group. There were also no differences in plasma CA levels after immobilization stress between the two groups. 5. With cold stress, plasma NA levels increased 5-fold and adrenaline levels by 3-fold over basal at 45 min in the vehicle pre-treated rats. This increase was not observed in the capsaicin group. 6. Immunoreactive substance P was depleted by only 68% in the splanchnic nerve following capsaicin pre-treatment. If the remaining 32% was biologically active substance P then it could account for the maintenance of the response to hypovolaemic and immobilization stress. However, it might be possible that the responses to hypovolaemic and immobilization stresses could be attenuated if a more complete depletion were achieved. 7. These results in conscious rats indicate that capsaicin-sensitive sensory neurons are required for plasma CA response to selective stressors. They are required for CA output in response to cold stress and to the early phase of swimming stress, but not to hypovolaemic stress and immobilization stress.
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PMID:Capsaicin-sensitive sensory neurons are involved in the plasma catecholamine response of rats to selective stressors. 184 48

In the present experiments the role of unmyelinated sensory fibres in the mechanism of cutaneous inflammatory reactions under normal and pathological conditions has been studied in man and animals. Dye leakage responses to histamine, serotonin, compound 48/80, bradykinin and substance P were significantly reduced, while neurogenic inflammation was completely abolished in rats treated neonatally with capsaicin, as studied quantitatively by the Evans blue technique. Neurogenic inflammation could also be elicited by mustard oil in normally innervated human skin, but not in skin areas affected by herpes zoster or in a patient suffering from congenital analgesia. Repeated topical treatment of the skin with capsaicin (local desensitization) abolished the neurogenic inflammatory response for several days. Chemical pain sensitivity was strongly reduced, and thresholds for warmth and heat pain sensations were significantly elevated. Local capsaicin desensitization of the skin prevented whealing, flare and itch in patients with acquired cold and heat urticaria. The findings indicate that peptide-containing sensory nerves are involved in the mediation of chemogenic and heat pain, and possibly itch, and are responsible for initiation of the neurogenic inflammatory response. The results also provide direct evidence of the involvement of these particular sensory nerves in the modulation of the permeability-increasing effects of putative mediators of acute inflammatory reactions. It is concluded that, through modulation of cutaneous vascular reactions, peptidergic sensory nerves may play a hitherto unrecognized role in the pathomechanism of certain diseases of human skin.
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PMID:The modulation of cutaneous inflammatory reactions by peptide-containing sensory nerves. 241 73

We have studied the involvement of sensory nerves containing substance P (SP) in the modulation of stress-induced catecholamine (CA) secretion from the sympathetic nervous system and adrenal medulla. Adrenaline and noradrenaline (NA) levels were measured in blood samples withdrawn from the inferior vena cava (i.v.c.) at 5 or 15 min intervals for periods of up to 60 min, in adult rats during stress induced by insulin or cold. Insulin stress caused a biphasic elevation of plasma CA. Previous studies from our laboratory have shown that the first phase lasting 30 min is neurogenic, and the second phase from 30 to 60 min is non-neurogenic in mechanism. In control adult rats (with normal levels of SP in their splanchnic nerve), insulin stress caused a slow and progressive secretion of adrenaline into the circulation for the first 30 min (neurogenic phase). In the period 30-60 min (non-neurogenic phase) plasma adrenaline and NA levels rose at a much higher rate. In capsaicin-pre-treated rats (in which SP levels in the splanchnic nerve were depleted by 68%) insulin stress produced a steady increase in plasma adrenaline levels for up to 5 min similar to that in insulin-stressed control animals; however, by 10 min the plasma adrenaline levels had fallen to basal and remained low up to 30 min. From 30 to 60 min, plasma adrenaline and NA levels rose steeply as seen with control animals. We conclude that capsaicin pre-treatment affected the neurogenic phase but did not affect the non-neurogenic phase. Cold stress increased the plasma adrenaline levels by a neurogenic mechanism over 30 min in control rats. In contrast, in capsaicin-pre-treated, cold-stressed rats, plasma adrenaline did not increase significantly. Plasma NA levels were also significantly lowered in capsaicin-pre-treated, cold-stressed rats during the neurogenic phase but NA increases were not dependent on an intact adrenal innervation. The results using both insulin stress and cold stress suggest that capsaicin-sensitive (sensory) nerve fibres in the adrenal medulla and in sympathetic ganglia are capable of modifying the secretory responses of these tissues to stress. Results from our previous in vitro work are compatible with the view that SP may be the neuromodulator released from such sensory nerves to produce these effects. This suggests that the previously reported ability of SP to modulate nicotinic receptor function in vitro by either inhibiting the nicotinic response or protecting against nicotinic desensitization may be more than a mere pharmacological curiosity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of sensory fibres in the rat splanchnic nerve in the regulation of adrenal medullary secretion during stress. 242 Sep 73

The presence of substance P in numerous mammalian pineal glands prompted us to search for its binding sites in the bovine pineal gland. The binding assays to pineal membrane were carried out in polypropylene microcentrifuge tubes in a final volume of 500 microliters of 50 mM Tris-HCl buffer (pH 7.4) containing aliquots of 200-500 micrograms protein, 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, and 50 microliters of [3H]substance P (3H-SP, 45.7 Ci/mmol to yield a final concentration of 0.02-20 nM) to start the reactions, which were incubated for 20 min at 20 degrees C. The reactions were terminated by centrifugation in a Fisher Microcentrifuge Model 235A for 30 seconds at 13,000 X g, and the pellets were washed twice with 1 ml of ice-cold 50 mM Tris-HCl buffer containing 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, and 1 mM CaCl2. The bottoms of the tubes were cut, the membrane pellets were dissolved in 5 ml of Triton X-100/toluene fluor (1:3) scintillation fluid, and the radioactivity was counted. The specific [3H]-substance P binding at 1-2 nM was 40-50% of the total binding, and the non-specific binding was assessed by using 2 microM of unlabelled substance P. These studies identified in bovine pineal gland a high affinity receptor site for [3H]SP with a KD value of 0.43 nM and a Bmax value of 71.14 fmol/mg protein. The relative affinity of various substance P analogues or fragments was: substance P greater than physalaemin greater than SP2-11 greater than SP3-11 greater than SP4-11 greater than SP6-11 greater than substance K = eledoisin greater than kassinin greater than SP7-11 greater than SP free acid. Substance P did not alter the basal or the norepinephrine-induced stimulation of the activity of serotonin N-acetyltransferase in rat pineal gland in culture.
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PMID:Studies on high-affinity [3H]substance P binding sites in bovine pineal gland. 243 Jul 88

Contractile responses to neurokinin alpha and neurokinin beta were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin alpha and neurokinin beta as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin greater than substance P = neurokinin alpha = neurokinin beta. After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin alpha greater than eledoisin greater than neurokinin beta much greater than substance P). From the Schild analyses, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin beta, and antagonized the response to neurokinin alpha and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.
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PMID:Pharmacological evidence for the possible coexistence of multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle. 243 60

Previous studies have demonstrated that the sensory neuropeptide substance P (SP) can modulate immune responses in vitro. Work from this laboratory has shown that SP enhances immunoglobulin synthesis by murine splenic and Peyer's patch lymphocytes stimulated with concanavalin A. One mechanism underlying these effects is the binding of SP to specific receptors on lymphocytes. We examined the distribution of SP receptors on murine T and B lymphocytes and their subsets by one and two color fluorescence-activated cell sorter analysis. The specificity and nature of binding was examined using radiolabeled SP, and competitive inhibition experiments were performed with cold SP. In cytofluorimetry experiments, both T and B lymphocytes from Peyer's patches and spleen were bound to SP, with those from Peyer's patches having a higher proportion than lymphocytes from the spleen. The majority of T cells from both organs bound SP with binding being evenly distributed between Lyt-1+ and Lyt-2+ cells. Similarly, the majority of B lymphocytes from spleen and Peyer's patches showed SP binding. There were no significant isotype-specific differences within any organ. Studies using 125I-labeled SP showed specific binding to all lymphocyte subpopulations examined. SP receptors were fewer in number on cells isolated from spleen than on cells from Peyer's patches although the dissociation constants were similar for all populations examined. These studies demonstrated that SP receptors are present both on murine T and B lymphocytes from Peyer's patches and spleen. There is no evidence for differential SP receptor expression on distinct lymphocyte subsets in spleen or Peyer's patches.
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PMID:Distribution of substance P receptors on murine spleen and Peyer's patch T and B cells. 243 91

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. The capsaicin-(1 microM) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4 degrees C). Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides.
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PMID:Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract. 244 29

Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.
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PMID:Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria. 244 38


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