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)

Proton magnetic resonance techniques were used to study the conformation of the synthetic tubulin fragment Ac-tubulin (430-441) amide in H2O and 80% CD3OH/20% D2O solutions, using water suppression techniques. Proton assignments are based on two-dimensional COSY experiments combined with one-dimensional spin decoupling. A comparison of the NH proton shifts between the two solvents, namely delta(CD3OH/H2O-H2O) shows a small solvent effect for the Lys1 to Val6 region of the molecule, whereas for Gly7 to Glu12 the solvent effect is much larger. The smaller effects in the region of Lys1 to Val6 may be due to some hydrogen bonding as these protons are shielded from the solvent. These conclusions are in agreement with the circular dichroism results in 80% methanol/20% water where the alpha helix is present to the extent of 30%, whereas the peptide is completely unstructured in water with some aggregation. The temperature dependence of the NH proton shifts was also carried out. In water these shifts are of the order of 7-9 X 10(-3) ppm/K indicating that most of the protons are not involved in hydrogen bonding. In CD3OH/H2O, these values range from about 4-6 X 10(-3) ppm/K, which are compatible with the presence of hydrogen bonds. Finally, binding studies were carried out between the tubulin peptide and the undecapeptide neutrotransmitter substance P. The largest shifts are for the Tyr3 NH proton of the tubulin fragment, whereas for substance P it is for the Lys3, Gln5 and Leu10 NH protons, indicating a change in conformation of both peptides on interaction.
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PMID:A proton magnetic resonance and a circular dichroism study of the solvent dependent conformation of the synthetic tubulin fragment Ac tubulin, alpha (430-441) amide and its interaction with substance-P. 248 63

Three N-terminal fragments of the neurotransmitter Substance P as well as two antagonist heptapeptides containing D-amino-acid residues were studied using different 1D and 2D NMR techniques. Total nonexchangeable 1H-NMR assignments were carried out in D2O and the NH protons were assigned in H2O by means of COSY experiments. The spectral data indicates that there are no preferred conformations for the backbone. The N-terminal tetrapeptide SP1-4-OH exists as a mixture of cis/trans isomers and this effect was studied as a function of pH.
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PMID:An NMR study of the conformations of N-terminal substance P fragments and antagonists. 248 53

Substance P (SP, 1.5 nmol) injected into the medial preoptic area (MPOA) of conscious, unrestrained, water-loaded male rats induced a significant decrease in urinary sodium, potassium and water excretion. In contrast, a significant natriuretic effect was observed after injection of 0.3 nmol of a specific competitive SP antagonist [( D-Pro2, D-Trp7,9]-substance P). SP partially blocked the carbachol-induced natriuresis in a time-dependent manner. These data indicate a tonic inhibitory action of SP on sodium excretion and suggest a putative modulatory action of SP on the cholinergic system.
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PMID:Substance P injected into the medial preoptic area inhibits sodium, potassium and water urinary excretion. Putative modulation of the cholinergic system. 248 31

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2-5% CO2) hyperpnea "challenges" were performed by increasing the tidal volume (2-6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.
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PMID:Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs. 249 85

Intracerebroventricular administration of eledoisin, the tachykinin peptide of the salivary glands of Eledone Moschata, exerts a potent and long-lasting inhibition of water intake induced by the subcutaneous administration of hypertonic NaCl in the rat. The inhibitory effect is statistically significant up to 6 hr following eledoisin treatment, while the 24 hr water intake in control and treated rats is essentially identical. The results of the present study demonstrate that the long-lasting effect is not due to increased renal excretion of the osmotic load, nor, likely, to larger production of metabolic water. Probably, eledoisin exerts an inhibitory effect of such a long duration by means of central actions which last well beyond its half-life, or, alternatively, by promoting an increased excretion of the osmotic load through elimination routes different from the kidney.
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PMID:[Effects of eledoisin on water intake induced by subcutaneous injection of hypertonic NaCl in the rat]. 253 90

In a previous study we investigated the effects of age on the micturition characteristics and bladder function of male Fischer rats ages five to seven, 16 to 18 and 22 to 24 months. The 24 hr. water intake and urine output increases significantly with age; 22 to 24 month rats showed a 39% increase in water intake and a 93% increase in urine output compared to five to seven month rats. The intravesical pressure at micturition is 100% greater in 22 to 24 month and 16 to 18 month rats compared to five to seven month old rats with no age-related change in bladder volume at micturition. In the present study, in vitro bladder capacity did not differ between the three age groups although the average plateau pressure significantly decreased with advancing age. Using the isolated whole bladder model, the contractile response to the autonomic agonists bethanechol, phenylephrine, and isoproterenol did not change significantly with age. Similarly, there were no age-related changes in the response of the bladder to non-autonomic drugs (histamine, oxytocin, serotonin, substance P, and PGF2 alpha) except for PGF2 alpha which produced an age-related increase in the maximum bladder contraction. In summary, while in vivo micturition clearly changes with age, the in vitro contractility of the bladders to autonomic agents did not. Therefore, age related differences in micturition would be related primarily to the changes in neuronal innervation and central control of micturition rather than alterations in the contractility of the bladder. In addition, these studies show the importance of correlating in vivo bladder function (micturition frequency and volume, cystometry and urodynamics) with in vitro contractile and functional studies.
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PMID:Effects of age on urinary bladder function in the male rat. 256 16

Nonadrenergic, noncholinergic (NANC) innervation, the third division of the autonomic nervous system, has both inhibitory and excitatory parts. The excitatory part received only limited attention. Substance P has been suggested to be the neurotransmitter of the excitatory part. The NANC-inhibitory innervation has recently been studied in detail. Although the neurotransmitter has not been conclusively identified, a substantial body of evidence exists to support vasoactive intestinal peptide (VIP) as the neurotransmitter. VIP is widely distributed in the body. Reports show that this innervation in animals and man plays a significant role in both health and disease. Pathological conditions could result from either an increase or decrease in VIP production. An absence of VIP-producing neurons has been identified to be responsible for Hirschsprung's disease in the alimentary system and hyperactive airways in the respiratory system. An increase in VIP production is associated with chronic water diarrhea syndrome in humans. Taking these factors into consideration, various therapeutic measures are suggested with the use of VIP or its antagonists.
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PMID:Vasoactive intestinal peptide (VIP), a putative neurotransmitter of nonadrenergic, noncholinergic (NANC) inhibitory innervation and its relevance to therapy. 256 97

The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth muscle functions, it is not known whether similar stimuli also influence salt and water transport as a meal traverses the alimentary canal.
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PMID:Intestinal nerves and ion transport: stimuli, reflexes, and responses. 257 77

The regional distribution of various forms of tachykinin-like immunoreactivity (TKLI) was studied in rat brain using radioimmunoassay. TKLI was measured with two different tachykinin-antisera (K12 and E7), which react with neurokinin A (NKA) and neurokinin B (NKB) but not with substance P (SP) and with a specific SP-antiserum. TKLI-K12 and TKLI-E7 were found to have similar regional distributions which were, however, significantly different from that of the substance P-like immunoreactivity (SPLI). Thus, the ratio of the tissue concentrations of TKLI-K12 or TKLI-E7 to that of SPLI was higher in frontal cortex and hippocampus and lower in pons/medulla oblongata than in the other regions studied. Cation-exchange chromatography of neutral water extracts of brain tissue revealed two major immunoreactive components of TKLI-K12 and TKLI-E7, one of which co-eluted with synthetic NKB while the other appeared in the same region as synthetic NKA. The relative quantities of these components varied depending on the brain region studied. No TKLI-K12 or TKLI-E7 co-eluted with synthetic SP. Almost all of the SPLI in acetic acid or water extracts of brain tissue eluted as a single chromatographic component in the same position as synthetic SP. Potassium-stimulated in vivo release of TKLI-K12, TKLI-E7 and SPLI in striatum of rat brain could be demonstrated using intracerebral dialysis. The present results imply that tachykinins, which may serve as neurotransmitters or neuromodulators, are present in different proportions in different regions of rat brain.
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PMID:Regional distribution and in vivo release of tachykinin-like immunoreactivities in rat brain: evidence for regional differences in relative proportions of tachykinins. 258 Dec 87

The effect of substance P on the metabolism of membrane phosphoinositides and the possible role of this effect in the contractile response to substance P was investigated in longitudinal muscle strips obtained from the guinea-pig small intestine and prelabelled with [3H] inositol. Substance P (2.2 microM) failed to change significantly the tissue content of phosphoinositides but caused an accumulation of their water-soluble hydrolysis products, inositol bisphosphate (InsP2) and inositol monophosphate (InsP). These experiments were carried out in the presence of Li+ (12 mM), since only under these conditions could an accumulation of InsP2 be observed. The rate at which InsP2 and InsP accumulated was highest during the first 0.5 min of exposure to substance P (2.2 microM) and then decreased rapidly. Thus, the rate of inositol phosphate accumulation paralleled the time course of the contractile response to substance P. The magnitude of inositol phosphate accumulation was related to the concentration of substance P (22 nM-22 microM). The substance P-induced accumulation of InsP2 and InsP was not reduced when muscle strips had been incubated in Ca2+-free medium, for a time period sufficient to deplete the intracellular Ca2+ store which can be released by substance P, or in Ca2+-free medium containing high [K+]. These findings are compatible with the concept that hydrolysis of membrane phosphoinositides is a mechanism that links substance P receptor activation to contraction but further work is needed to establish a causal relationship.
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PMID:Substance P action on phosphoinositides in guinea-pig intestinal muscle: a possible transduction mechanism? 258 78


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