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)

A new glycopeptide analogue of substance P (6-11) (SP6-11), namely, N1,6 (beta-D-glucopyranosyl) [Glu6, Pro9]SP6-11, has been synthesized and found to be water soluble. The in vitro biological activity of this glycopeptide was determined for spasmogenic activity in the guinea pig ileum and for potentiation of electrically evoked contractions in the rat vas deferens. Thus, activities on NK-1, NK-2, and NK-3 receptor types have been differentiated by two assays and, in the case of NK-1 and NK-3, receptors in guinea pig ileum (GPI) were assayed using specific pharmacological procedures. The ED50 values for the analogue and reference peptides substance P (SP), neurokinin A(NKA), and neurokinin B (NKB) were determined and potencies relative to SP were calculated. The analogue is three times more potent than the potent NK-1 agonist SP on NK-1 receptors. Moreover, this glycopeptide proved to be as selective for the NK-1 receptor as the specific agonist SPOMe (the methyl ester of substance P).
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PMID:A synthetic glycopeptide of substance P analogue (SP6-11) with enhanced NK-1 receptor specificity. 169 Feb 89

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

The effect of thermal stimulation on primary afferent neurons and its modulation by Ruthenium Red (RR) has been investigated in the isolated perfused rabbit ear with intact neuronal connection to the animal. Capsaicin, K(+)-depolarization as well as increasing the temperature of the perfusate to 50 degrees C, increased the amount of substance P-like immunoreactivity (SP-IR) in the outflow in a calcium-dependent manner. High performance liquid chromatography (HPLC) revealed that SP-IR which was released by thermal stimulation consisted of two components, one of which co-eluted with synthetic substance P. The same two components of SP-IR were also present in extracts of the auricular nerve and were released by capsaicin. RR attenuated the effect of capsaicin and thermal stimulation but did not reduce potassium-evoked release of SP-IR. To evaluate an inhibitory action of RR on the excitation of primary afferents, the isolated perfused ear with intact neuronal connection to the anaesthetized rabbit was used. Intraarterial injection of capsaicin or bradykinin as well as superfusion of a skin area of approximately 2 cm2 with water at 53 degrees C for 1 min, produced a depressor reflex. RR attenuated the response to thermal stimulation and to capsaicin, but did not block the bradykinin-induced depressor reflex. These results demonstrate that, in the rabbit ear, thermal stimuli excite primary afferent neurons and evoke the calcium-dependent release of neuropeptides from their peripheral terminals by a mechanism which is sensitive to RR.
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PMID:Activation of primary afferent neurons by thermal stimulation. Influence of ruthenium red. 169 Mar 58

In the present study characterization of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PIP2-PLC) activity and receptor-mediated hydrolysis of PIP2 in rat anterior pituitary membranes were investigated. Incubation of the membrane fraction of anterior pituitary homogenate with [3H]inositol-labeled PIP2 in the presence of calcium increased the concentration of the water-soluble degradation product inositol trisphosphate (IP3) in a time-dependent manner. PIP2-PLC in the rat anterior pituitary had a pH optimum at 5.5 and a requirement for cations. Ca2+ and Mg2+ could activate the enzyme. Activity was maximal at a total magnesium concentration of 1 mM and at a free Ca2+ concentration of 100 microM. The addition of the detergent Triton X-100 (0.05% w/v) to the membrane fraction resulted in a 50% decrease of PIP2-PLC activity, whereas the presence of sodium deoxycholate (1 mg/ml) in the membrane fraction increased the PIP2-PLC activity by 100%. The tachykinins substance P, 8-Tyr-substance P, physalaemin, neurokinin A, eledoisin, kassinin and neurokinin B induced receptor-mediated breakdown of [3H]inositol-labeled PIP2 in the membrane fraction in a concentration-dependent manner, but with different potencies. The tachykinins displayed the following rank order of potencies: substance P greater than 8-Tyr-substance P greater than physalaemin greater than neurokinin A greater than eledoisin greater than kassinin greater than neurokinin B, which is consistent with the involvement of a NK-1 receptor. Combined treatment of anterior pituitary membranes by substance P and thyrotropin-releasing hormone (TRH) resulted in an additional increase in PIP2-PLC activity compared to stimulation with TRH alone.
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PMID:Substance P and related tachykinins induce receptor-mediated hydrolysis of polyphosphoinositides in the rat anterior pituitary. 169 Nov 15

Previous studies in the ferret demonstrated that vagal nerve stimulation induced an atropine-resistant water secretion. Substance P and vasoactive intestinal polypeptide are possible mediators of this secretory response. The objectives of this study were to investigate the in vivo effects of substance P and vasoactive intestinal polypeptide on the jejunal musculature and epithelium. Substance P caused an increase in jejunal motility, water secretion, and transmural potential difference. Cholinergic blockade did not affect the substance P-induced contractions, but did reduce the increase in transmural potential difference, suggesting an inhibition of water secretion. Vasoactive intestinal polypeptide abolished motor activity; however, it induced an increase in transmural potential difference that was atropine and tetrodotoxin resistant. By immunohistochemical methods, immunoreactive vasoactive intestinal polypeptide and immunoreactive substance P were localized to both nerve cell bodies and nerve fibers in the ferret intestine. Determination of intestinal concentrations of vasoactive intestinal polypeptide and substance P in the ferret showed concentrations of these two neuropeptides that were similar to those in human intestine and demonstrated much higher concentrations of these substances in the muscular layer than in the epithelial layer. Our data demonstrate that in the ferret substance P excites and vasoactive intestinal polypeptide inhibits jejunal motor activity. However, both peptides increase water secretion. Our results suggest that in response to vagal stimulation, neuronally released substance P or vasoactive intestinal polypeptide may participate in the atropine-resistant water secretion.
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PMID:Effects of substance P and vasoactive intestinal polypeptide on contractile activity and epithelial transport in the ferret jejunum. 169 48

The effects of the peripherally administered neuropeptide substance P (SP) on spatial learning capacities were investigated in 27-month-old rats using a water-maze task. Old rats were injected intraperitoneally once daily for 6 days with 50 or 250 micrograms/kg SP or vehicle 30 min prior to acquisition trials. Improvement in maze performance was observed following injections of 250 micrograms/kg SP only. Furthermore, vehicle-treated old rats showed significantly poorer acquisition rates than vehicle-treated 12-week-old rats. Thus, the improvement in performance after the 250 micrograms/kg dose of SP can be interpreted in terms of a compensation of performance deficit in the old rats.
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PMID:Neuropeptide substance P improves water maze performance in aged rats. 169 2

The interaction between lipids and water soluble amphiphiles was investigated by means of a monolayer technique, monitoring the area increase at constant surface pressure. The area increase could be quantitated and binding isotherms at different surface pressures were measured. A comparison of dibucaine binding to monolayers and bilayers showed that a surface pressure of 32 mN/m best represents the packing density in a lipid bilayer (Seelig, 1987). Binding isotherms measured for charged dibucaine and substance P (SP) were analyzed by means of two different models. If electrostatic effects were ignored the binding of dibucaine and SP showed biphasic Scatchard plots. If, however, electrostatic effects were taken into account by means of the Gouy-Chapman theory, the insertion of both amphiphiles was best described in terms of a partitioning into the monolayer lipids. The hydrophobic binding constant was Kp = 660 +/- 80 M-1 for charged dibucaine inserting into coarse liposomes or monolayers at 32 mN/m (Seelig et al., 1986) and 1-1.8 M-1 for SP inserting into monolayers at 32 mN/m (Seelig and Macdonald, 1989).
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PMID:The use of monolayers for simple and quantitative analysis of lipid-drug interactions exemplified with dibucaine and substance P. 169 84

Taste receptor organ activity and preference of sodium chloride solution in rats with deficit of substance P (SP) were studied. Total impulse activity of chorda tympani nerve of 7-8 week old rats was recorded under nembutal anesthesia. The taste responses to four solutions (sucrose, quinine sulfate, sodium chloride and citric acid) were decreased in rats injected with capsaicin in comparison with rats injected with vehicle. The rats injected with capsaicin preferred water to sodium chloride (two-bottle technique). On the contrary the rats injected with capsaicin preferred the salt solution. These data together with previous studies show the important role of peptide SP in taste receptor activity and "salt appetite".
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PMID:[Changes in the activity of the taste receptor apparatus and the preference for a sodium chloride solution in newborn rats receiving capsaicin]. 169 97

One of the major target organs of hydrogen sulphide gas is the lung. Exfoliation of upper respiratory epithelia and pulmonary edema are prominent effects. Various neuropeptides contained in afferent C-fibres are intimately associated with the epithelia of the conducting airways and are liberated upon exposure to noxious gases. We sought to determine their role in the pathogenesis of hydrogen-sulphide-induced pulmonary injury by pretreating rats with the neurotoxin, capsaicin, which is known to ablate a subpopulation of vagal afferent C-fibres. Groups of capsaicin and saline (control) pretreated Fischer 344 rats were exposed to an edemogenic concentration of hydrogen sulphide (525-559 mg/m3) for 4 hr. Mortality was significantly greater (p less than 0.01) in the capsaicin treated rats (12/12) compared to the control animals (2/12). Pulmonary injury was also more severe in the capsaicin pretreated animals as assessed by lung water content, histological grade of pulmonary edema and protein in the broncho-alveolar fluid. Animals depleted of substance P exhibited a significantly greater (p less than 0.01) degree of bronchial epithelial cell exfoliation and ulceration following exposure to hydrogen sulphide. These experiments indicate that capsaicin sensitive sensory nerves may play a major role in pulmonary defense against the effects of inhaled toxic gases such as hydrogen sulphide.
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PMID:Capsaicin pretreatment modifies hydrogen sulphide-induced pulmonary injury in rats. 169 78

Human skin mast cells release histamine in response to both immunologic stimulation mediated by anti-IgE and IgE-independent mechanisms of which substance P is a prototypical secretagogue. We compared the ultrastructural changes produced in dissociated foreskin mast cells by these two stimuli with histamine release. Mast cells were isolated and pooled from the foreskins of 2- to 7-year-old boys in four separate experiments and comprised 25 to 60% of the total dissociated cells. The secretory granules in resting mast cells comprised 47.5% of the extranuclear cell volume and contained crystalline structures, namely, scrolls, gratings, and lattices, in an electron-dense matrix. Stimulation with either anti-IgE or substance P resulted in a net histamine release of 10.2 +/- 1.7% or 21.4 +/- 4.0%, respectively. After either secretagogue, about 75% of the cells underwent compound exocytosis, with fusion of the granule membranes with one another and with the plasma membrane to produce large degranulation channels that opened to the extracellular space. The granules lost their crystalline structure and electron density during secretion but retained the round shape of the original granule as a core that subsequently formed a fibrillar residue. Degranulation channels occupied 30 to 60% of the cytoplasmic volume after substance P stimulation and 10 to 40% after anti-IgE, which compared well with the greater histamine release measured after substance P. The rapid increase in the volume of the degranulation channels after substance P was accompanied by a decrease in cytoplasmic volume, suggesting water moved from the cytoplasm into the granules after stimulation. This study shows that secretion produced in dissociated human foreskin mast cells by two different stimuli, anti-IgE and substance P, which act through different membrane receptors and have distinct secretory characteristics, is similar morphologically.
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PMID:Dissociated human foreskin mast cells degranulate in response to anti-IgE and substance P. 170 Jan 94


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