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)

In anesthetized rats, we examined whether inhibitory renorenal reflex responses to renal pelvic mechanoreceptor (MR) and chemoreceptor (CR) stimulation were mediated by substance P (SP)-containing neurons. Capsaicin (0.5 ng to 5 micrograms) injected into the renal pelvis increased afferent renal nerve activity (ARNA) dose dependently, from 60 +/- 19 to 333 +/- 105%. For a given ARNA response, a 100-fold higher dose was required when capsaicin was injected into the renal interstitium compared with the renal pelvis. Renal pelvic administration of SP (25 ng) increased ipsilateral ARNA by 126 +/- 34% and contralateral urine flow rate and urinary sodium excretion by 21 +/- 4 and 28 +/- 7%, respectively, a response similar to that produced by renal MR and CR stimulation. Mean arterial pressure was unaffected. Ipsilateral renal denervation abolished the contralateral diuresis and natriuresis produced by SP. In rats treated with capsaicin (950 mg/kg subcutaneously over 1 wk) to deplete sensory neurons of SP, renal MR and CR stimulation failed to elicit a renorenal reflex response. The data suggest that the renorenal reflex responses to renal MR and CR stimulation are mediated at least, in part, by SP neurons or other sensory neurons susceptible to depletion by capsaicin.
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PMID:Inhibitory renorenal reflexes: a role for substance P or other capsaicin-sensitive neurons. 170 97

The effects of inhaled bradykinin (BK), substance P (SP), and neurokinin A (NKA) on pulmonary resistance and airway responsiveness to carbachol were studied in conscious allergic sheep. Inhaled BK (20 breaths, 0.1 to 5.0 mg.ml-1) caused dose-dependent increases in pulmonary resistance. Neither inhaled SP nor NKA (20 breaths, 0.1 to 1.0 mg.ml-1) produced significant bronchoconstriction in allergic sheep. However, the response to SP could be enhanced (p less than 0.05) by pretreatment with the neutral endopeptidase inhibitor, thiorphan (40 breaths, 1 mg.ml-1). Sheep that were allergic to Ascaris suum antigen were 5.9 times (p less than 0.05) more sensitive to the constrictor effects of BK than nonallergic sheep. BK-induced bronchoconstriction was blocked in a dose-dependent fashion by the BK beta 2-receptor antagonist, NPC 567 (D-arginine[hydroxyproline3,D-phenylalanine7]BK). Atropine (0.2 mg.kg-1, intravenously) and nedocromil sodium (1 mg.kg-1 in 3 ml of saline, aerosolized) significantly inhibited the BK-induced bronchoconstriction by 97% and 43%, respectively. Chlorpheniramine (2 mg.kg-1, intravenously) had no effect. NKA caused a transient increase in airway responsiveness in allergic sheep, producing a mean 1.9-fold leftward shift in dose-response curves to aerosolized carbachol (p less than 0.05). This hyperresponsiveness was not evident 24 hours after NKA challenge. Neither SP nor BK changed airway responsiveness. Thus, in allergic sheep, inhaled BK caused a more pronounced bronchoconstriction than that observed in nonallergic sheep. The bronchoconstriction was blocked by a BK-receptor antagonist and appeared to be partially mediated via cholinergic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. 170 88

Addition of the neuropeptide galanin to small cell lung cancer (SCLC) cells loaded with the fluorescent Ca2+ indicator fura-2-tetraacetoxymethylester causes a rapid and transient increase in the intracellular concentration of Ca2+ ([Ca2+]i) followed by homologous desensitization. Galanin increased [Ca2+]i in a concentration-dependent fashion with half-maximum effect (EC50) at 20-22 nM in H69 and H510 SCLC cells. Galanin mobilized Ca2+ from intracellular stores since its effects on [Ca2+]i were not blocked by chelation of extracellular Ca2+. Pretreatment with pertussis toxin (200 ng/ml for 4 h) did not prevent galanin-induced Ca2+ mobilization. In contrast, direct activation of protein kinase C with phorbol esters attenuated the Ca2+ response induced by galanin. The effects of galanin could be dissociated from changes in membrane potential: galanin did not increase membrane potential in SCLC cells loaded with bis(1,3-diethyltiobarbiturate)-trimethineoxonol and induced Ca2+ mobilization in depolarized SCLC cells, i.e., in cells suspended in a solution containing 145 mM K+ instead of Na+. Galanin also caused an increase in the formation of inositol phosphates in a time- and dose-dependent manner (EC50 10 nM). A rapid increase in the inositol trisphosphate fraction was followed by a slower increase in the inositol monophosphate fraction. Galanin stimulated clonal growth of both H69 and H510 cells in semisolid (agarose-containing) medium. This growth-promoting effect was sharply dependent on galanin concentration (EC50 20 nM) and markedly inhibited by [Arg6,D-Trp7,9,MePhe8]substance P, a recently identified broad spectrum neuropeptide antagonist. The results show for the first time that galanin receptors are coupled to inositol phosphate and [Ca2+]i responses in SCLC cells and, in particular, that this neuropeptide can act as a direct growth factor for these human cancer cells.
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PMID:Galanin stimulates Ca2+ mobilization, inositol phosphate accumulation, and clonal growth in small cell lung cancer cells. 170 78

In adult animals, airway fluid secretion is enhanced reflexly via central nervous system pathways, and locally by mediators such as substance P. To evaluate the role of maturation on these regulatory mechanisms, we compared the effects of reflex stimulation and intravenous substance P administration on airway secretion in anesthetized, paralyzed and artificially ventilated piglets, 9 to 22 days of age, and older piglets all aged 10 weeks. Airway secretion was monitored by counting the hillocks appearing in the upper trachea in an exposed field of tracheal epithelium (1.2 cm2) coated with powdered tantalum. In younger animals, mechanical stimulation of the larynx had no discernible effect on tracheal submucosal gland secretion. Neither excitation of airway irritant receptors nor stimulation of pulmonary C-fiber receptors by capsaicin caused a significant increase of fluid secretion from tracheal submucosal glands. In addition, stimulation of peripheral chemoreceptors by ventilating animals with 12% O2 in N2, and 6% O2 in N2, failed to induce a substantial change in airway secretion, when compared with number of hillocks in the control period. Furthermore, administration of sodium cyanide had little or no effect on baseline secretion. In contrast, to the weak reflex responses in younger piglets electrical stimulation of the vagus nerve caused the number of hillocks to increase on average by 16.3 +/- 2.3 (P less than 0.01). In addition, local application of a pledget soaked in solution of methacholine caused the number of hillocks to increase by 32.1 +/- 5.2 (P less than 0.01). Intravenous administration of substance P also induced an augmentation in fluid secretion. Increase in concentration of substance P (10(-8), 10(-7), 10(-6), and 10(-5) M, 1 ml) was associated with a concomitant elevation in the number of activated submucosal glands (5.3 +/- 2.6, 10.0 +/- 4.4, 27.1 +/- 4.5, 41 +/- 5). In older piglets, stimulation of laryngeal mucosa, airway irritant receptors, as well as stimulation of pulmonary C-fiber receptors induced a significant increase in tracheal secretion, although stimulation of peripheral chemoreceptors had no effect on airway secretion. These data suggest that reflex responses of submucosal glands are weak during early postnatal development, however, tracheal submucosal glands do respond to exogenously administered cholinergic substances and tachykinin peptides.
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PMID:Reflex and chemical responses of tracheal submucosal glands in piglets. 170 84

Microiontophoresis of acetylcholine onto cheek pouch arterioles of the pentobarbital-anesthetized hamster results in both a local response at the pipette tip and a conducted dilator response. The conducted response is not dependent on blood flow, and its magnitude decays with distance from the site of stimulation. In an attempt to define the mechanism responsible for activation of arteriolar conduction, vasoactive agonists directed toward different vascular wall cell types, receptor types, and second messengers were applied to arterioles by pressure-pulse microejection. As expected, microapplication caused a consistent arteriolar response at the site of application with each of the agonists tested (local response). However, a high degree of variability was observed among agonists in their ability to produce conducted responses. Acetylcholine, muscarine, and phenylephrine, invariably induced both local and conducted responses. In contrast, bradykinin, substance P, papaverine, isoproterenol, and adenosine, though consistently inducing local responses, displayed a highly variable ability to induce the conducted responses. When conduction was observed, the arteriolar response was similar regardless of the agonist used to induce the response. Microejection of sodium nitroprusside or arginine vasopressin produced local arteriolar responses with no evidence of a conducted response regardless of the dose. These studies reveal previously undetected heterogeneity among microvessel responses and may reflect variations in the coupling mechanisms linking the local vasomotor response to the conducted response.
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PMID:Heterogeneity in conducted arteriolar vasomotor response is agonist dependent. 170 43

We compared histamine release induced by substance P with those obtained with classical secretagogues on human basophils, lung and skin fragments. We also tested the capacity of nedocromil sodium and theophylline to inhibit histamine release in these 3 experimental models. Substance P (10(-4) M) caused a noncytotoxic histamine release (about 10% of total) from basophils, lung and skin fragments. Substance P-induced histamine release was always smaller than that obtained with optimal doses of anti-IgE, formyl-methionine phenylalanine or compound 48/80. Nedocromil sodium did not prevent secretagogue-induced histamine release from basophils or sliced skin. In contrast, it significantly inhibited anti-IgE- or substance P-induced histamine release from human lung. Theophylline caused a dose-related inhibition on these 3 models. We conclude that substance P is a modest secretagogue for human basophils and mast cells, and that skin and lung mast cells are heterogeneous with respect to their response to nedocromil sodium.
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PMID:Substance P-induced histamine release from human basophils, skin and lung fragments: effect of nedocromil sodium and theophylline. 170

1. Multiple distinct affinity states or sites of substance P (SP) receptors exist in freshly-prepared rat brain membranes. 2. Substance P receptors may couple with islet-activating protein (pertussis toxin) sensitive GTP-binding protein(s). 3. Substance P receptors may be regulated Mg2+ and Na+ in an opposite manner. 4. Some important factor(s), in addition to GTP-binding protein, appear to be involved in SP binding activity. 5. An apparent molecular weight of the SP binding site is approximately 46,000 Da.
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PMID:Substance P receptors in mammalian central nervous system. 170 76

The effects of substance P (SP) on microvessels in the cremaster of sodium pentobarbital-anesthetized male, Sprague-Dawley rats were investigated using closed-circuit television microscopy. Topically added SP (bath concentrations of 10(-13) to 10(-8) M) caused significant dilation of small arterioles. SP vasodilation was sensitive to pretreatment of the muscle tissue with SP analogues, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (APTL-SP) and [D-Pro2, D-Trp7,9]-substance P (PT-SP). Attenuation of the responses by pyrilamine suggests that part of the SP-induced dilation involves the release of histamine. The vasodilation was abolished by hydroquinone, suggesting an intermediate role for endothelium-derived relaxing factor in the response to SP.
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PMID:Substance P mechanisms in the regulation of striated muscle microcirculation. 171 Nov 43

1. Sensory neuropeptides such as substance P may be implicated in the pathophysiology of asthma. 2. It has been proposed that nedocromil sodium may inhibit the effects of neuropeptides. 3. In this study, using an isolated innervated preparation of rabbit trachea, substance P, 10(-6) M, potentiated contractions induced by parasympathetic stimulation. The effect of substance P at the preganglionic site (307 +/- 38% of control, n = 5), was similar to that at the postganglionic site (307 +/- 61% of control, n = 5). 4. Nedocromil sodium, 10(-7) M, significantly inhibited the substance P-induced potentiation preganglionically (199 +/- 44%, n = 4, P less than 0.05) but not postganglionically (356 +/- 118%, n = 4). 5. These results suggest that nedocromil sodium may modify neuropeptide action selectively at a preganglionic site and that this may contribute to its therapeutic efficacy.
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PMID:Nedocromil sodium inhibits substance P-induced potentiation of cholinergic neural responses in the isolated innervated rabbit trachea. 171 86

myo-Inositol uptake in prisms of rat parotid glands was investigated by measuring both the accumulation of free myo-[3H] inositol into the cytosol and its incorporation into phospholipids. Total myo-[3H]inositol uptake involved two distinct processes, a prominent one which is saturable and sodium-dependent (Km, 95 microM; Vmax, 8 pmol/mg of protein per min) and a minor one, nonsaturable and sodium-independent. Phloretin and cytochalasin B, two inhibitors of hexose transport, and D-glucose, but only at high concentrations (greater than 10 mM), inhibited myo-[3H]inositol uptake. Dixon plots of the data indicated that D-glucose inhibition was noncompetitive suggesting that myo-inositol and D-glucose are transported by different carriers. Electrogenic cotransport of sodium and myo-inositol, rather than energy derived from mitochondrial oxidative metabolism, seems to be involved in the transport process. Thus, ouabain, monensin or veratridine, all of which increase intracellular sodium concentrations, reduced myo-[3H]inositol uptake, whereas dinitrophenol, potassium cyanide and carbonyl cyanide m-chlorophenyl hydrazone were without effect. Substance P affected only the sodium-dependent uptake process of myo-[3H]inositol, this inhibitory effect requiring extracellular calcium. Similar observations were made with the muscarinic agonist carbachol. From these results, an increase in intracellular sodium concentration linked to the activation of calcium-sensitive cation-permeant channels appears to be responsible for the inhibitory effects of substance P and carbachol on myo-[3H]inositol uptake, these effects being mediated respectively by NK1 and muscarinic receptors coupled to a phospholipase C.
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PMID:Inhibitory effects of substance P and carbachol on the saturable sodium-dependent uptake process of myo-inositol in rat parotid gland. 171 64


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