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 the superfused isolated rat urinary bladder, capsaicin as well as electrical field stimulation evoked the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP, threshold 2 microM) reduced both, the capsaicin- and the electrical field stimulation-evoked release of CGRP-IR while a low concentration of Ruthenium Red (RR, 0.6 microM and 2 microM) selectively attenuated the capsaicin-evoked release of CGRP-IR but did not influence the effect of electrical field stimulation. 20 microM RR nearly abolished the capsaicin-evoked release, but also attenuated the effect of electrical field stimulation. In the isolated guinea-pig bronchus, electrical field stimulation and capsaicin induced non-cholinergic contractions which are known to be caused by tachykinin release from afferent nerve terminals. CCCP (0.6 microM) only reduced the response to field stimulation; a ten-fold higher concentration of CCCP attenuated field stimulation as well as capsaicin-induced contractions. This is in contrast to the reported selective inhibition of capsaicin-induced contractions by RR. The present data demonstrate that CCCP generally inhibits evoked neuropeptide release, regardless of the kind of stimulation used while low concentrations of RR preferentially inhibit capsaicin-evoked neuropeptide release.
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PMID:Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones. 169 4

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

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

Previous studies have suggested that substance P (SP) may play a role in the carotid chemoreceptor response to hypoxia. Given the data from these studies we speculated that within the carotid body hypoxia might release SP which then acts on the chemosensitive unit. Concomitantly SP might be released in the superior cervical ganglion (SCG) and increase sympathetic outflow to the carotid body by interacting with acetylcholine in the SCG. The resulting vasoconstriction in the carotid body would further increase neural output from the carotid body. Hence we hypothesized that the exogenous SP on the carotid chemoreceptor neural activity would decrease after eliminating preganglionic inflow into the SCG. The hypothesis was tested using anesthetized, paralyzed and artificially ventilated cats. Neural activity from the carotid body (carotid chemoreceptor activity) or from the SCG (ganglioglomerular efferent nerve activity (GGN)) was measured. Close intra-arterial administration of SP (10 micrograms) caused a sustained stimulation of the carotid chemoreceptor activity which was accompanied by a fall in arterial blood pressure. The magnitude and time-course of the carotid body responses were extremely variable among the cats. The duration of increased chemoreceptor activity was significantly shortened after a transection of the cervical sympathetic nerve (CVSN). As a control, the duration of carotid body stimulation produced by the second injection of SP in a group of sham-operated cats was measured. This was essentially the same as the first injection, suggesting that the tachyphylactic effect of SP was negligible. The effects of the commonly used pharmacological agents (nicotine, cyanide, dopamine) on carotid chemoreceptor activity were not affected by the transection of the CVSN, GGN activity was also increased by exogenous SP. These results suggest that the effect of exogenous SP on carotid chemoreceptor activity consists of two components: (1) an initial direct excitatory effect; (2) a slowly developing excitatory effect mediated by the sympathetic outflow to the carotid body. The effects could be augmented by the accompanying hypotension.
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PMID:Sympathetic influence on carotid chemoreceptor response to substance P in the cat. 171 58

The effects of beta-endorphin, vasoactive intestinal polypeptide (VIP) and cholecystokinin octapeptide (CCK-8) on carotid chemoreceptor activity have been investigated in cats anaesthetized with pentobarbitone. Spontaneous chemoreceptor discharge was decreased by intracarotid injection of beta-endorphin and by low doses of VIP, whereas it was increased by CCK-8 and higher doses of VIP, these effects being relatively long-lasting and often associated with changes in systemic blood pressure. The chemoexcitation evoked by acetylcholine and sodium cyanide was reduced during intracarotid infusion of any of the three peptides studied, and that caused by CO2-saturated Locke solution was reduced by beta-endorphin, largely unaltered by VIP and variably affected by CCK-8. The inhibitory effect of beta-endorphin was greatly reduced by naloxone, implying that it probably involved actions at naloxone-sensitive opiate receptors in the carotid body. Substance P was unable to overcome the chemoinhibitory effect of methionine enkephalin. Possible functions of polypeptides in the carotid body are discussed.
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PMID:Effects of beta-endorphin, vasoactive intestinal polypeptide and cholecystokinin octapeptide on cat carotid chemoreceptor activity. 616 57

Coronary artery contractility is well known to be modulated by oxygen partial pressure. Both smooth muscle and the endothelium contribute to coronary artery oxygen sensitivity. Mechanisms underlying endothelium-dependent effects of oxygen include the sensitivity of the nitric oxide/endothelium-derived relaxing factor (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we characterize a novel endothelium-dependent component of porcine coronary artery oxygen sensitivity that is independent of these known pathways. Porcine coronary arteries were stimulated with either KCl or U46619. Hypoxia elicited a transient increase in force that was much greater in endothelium-intact arteries. This effect was abolished by nitric oxide/EDRF pathway inhibitors NG-monomethyl-L-arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric force to a similar degree in both intact and denuded arteries. Reoxygenation elicited a rapid and transient relaxation only in intact arteries. In contrast, this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways, such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol, or ouabain. The reoxygenation relaxation was, however, sensitive to very low levels of oxygen and was inhibited by cyanide and rotenone, suggesting an involvement of mitochondrial metabolism. Interestingly, the relaxation response to reoxygenation, similar to that for substance P, could be restored in denuded arteries by coupling with an endothelium-intact donor artery. This "sandwich" experiment suggests that the endothelium dependence is mediated by a transmissible factor. Our results indicate that a novel class of endothelium-dependent factors may contribute to coronary artery responses to changes in oxygen partial pressure.
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PMID:Reoxygenation-induced relaxation of coronary arteries. A novel endothelium-dependent mechanism. 815 34

Hypoxia has major effects on endothelium-dependent relaxation. To further understand the underlying mechanism(s), we investigated the O2 dependence of the endothelium-dependent relaxations elicited by ionophore A-23187 or agonists substance P (SP) or thrombin (TB) in porcine coronary arteries. A-23187 elicits an endothelium-dependent relaxation of KCl- or U-46619-induced contractures that can be described in terms of a rapid and slow phase. The duration of the relaxation was dose dependent. SP (10 nM) and TB (0.1 U/ml) also elicited endothelium-dependent relaxations that were rapid but transient. Hypoxic conditions (95% N2-5% CO2 instead of 95% O2-5% CO2; PO2 < 1%) abolished the A-23187 rapid phase and the SP and TB transient relaxation but not the A-23187 slow phase. Threshold PO2 for the rapid phase was approximately 35 mmHg. Pretreatment with cyanide (5 mM), to inhibit respiration, or 2-deoxy-D-glucose, to inhibit glycolysis, had little effect. Similarly, propranolol (10 microM) or indomethacin (10 microM) had no effect on the relaxation to A-23187, TB, or SP. In contrast, both NO synthesis inhibitors and ouabain blunted all endothelium-dependent relaxations studied. Our results suggest that the rapid relaxations to A-23187, SP, and TB are sensitive to O2 but not mitochondrial respiration. The slow sustained relaxation induced by A-23187, however, is characterized by a sensitivity to O2 that is distinct from that of the rapid phase, yet is dependent on an intact endothelium and is affected by NO synthesis inhibitors. Thus the endothelium-dependent relaxation to A-23187 is probably mediated by NO, but its sensitivity to O2 suggests that two distinct mechanisms may be involved.
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PMID:Dependence of endothelium-mediated relaxation on oxygen and metabolism in porcine coronary arteries. 834 45

Cyanide (CN) is a well-recognized poison whose complete actions are unclear. It has been shown that a vasoactive role may be partially responsible for the toxic effects of CN. Sodium nitrite, a known methemoglobin former and vasodilator, has been used to treat CN toxicity. It is rapidly transformed to nitric oxide (NO) which is thought to be endothelium-derived relaxing factor (EDRF). Since the literature suggests that NO can influence the biological effects of CN, studies were undertaken to determine if compounds known to release EDRF/NO will modify CN toxicity. Mice were administered a series of compounds which act through EDRF/NO release. These substances included, platelet-activating factor (PAF), hydralazine, bradykinin, histamine, calcium ionophore A23187, carbachol, or substance P at 0.060, 98.7, 50.0, 125, 1.0, 2.26, and 1.0 mg/kg, respectively. As a control, NG-monomethyl-L-arginine (NMA) 70 mg/kg, which inhibits NO synthesis, was administered to mice iv (tail vein) in combination with each test compound. All test compounds and NMA were administered prior to NaCN: NMA, 5 min; carbachol, 0.5 min; hydralazine, 0.5 min; bradykinin, 1 min; histamine, 1 min; substance P, 4 min; PAF, 5 min; and A23187, 5 min. Dose-response relationships were analyzed by probit dose-response methods and protective ratios for each compound were computed. Results suggest (i) that a portion of the action of CN is affected by a particular EDRF/NO-releasing compound, suggesting that each drug specifically affects regional EDRF/NO receptor sites, and (ii) that NO can play a role as a component in CN intoxication. It is suggested that CN does not act uniformly on all EDRF/NO receptor sites to produce toxicity and site-specific EDRF/NO agents may be useful for treating CN.
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PMID:The effects of EDRF/NO releasers or calcium ionophore A23187 on cyanide toxicity in mice. 880 52

Histamine (60 microM) produced ATP release from segments of guinea-pig vas deferens which was blocked by pyrilamine and triprolidine, H1-blockers, but not by ranitidine, an H2-blocker. The evoked-release was inhibited by the mitochondrial inhibitors, carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and oligomycin. Bradykinin (BK) and substance P (SP) also caused substantial and moderate release of ATP, respectively. The BK-evoked release of ATP was inhibited by HOE140, a B2-antagonist, but not by [Des-Arg10] HOE140, a B1-antagonist. On the other hand, VIP, angiotensin II (AII) and cholecystokinin-octapeptide (CCK-8) failed to elicit a measurable release of ATP. Histamine and BK also enhanced the release of ATP from superfused cultured smooth muscle cells. These results suggest that ATP may be released as an autacoid from the smooth muscles in the presence of these chemical mediators.
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PMID:ATP release caused by bradykinin, substance P and histamine from intact and cultured smooth muscles of guinea-pig vas deferens. 955 Feb 94

1. The effect of microinjecting angiotensin II (ANGII) into the nucleus of the solitary tract (NTS) on both baroreceptor and peripheral chemoreceptor reflexes was compared. 2. Experiments were performed in a working heart-brainstem preparation of rat. Baroreceptors were stimulated by raising perfusion pressure and chemoreceptors were activated with aortic injections of sodium cyanide (0.025 %, 25-75 microl). Reflex changes in phrenic nerve activity and heart rate were measured after bilateral NTS microinjection (50 nl) of ANGII (0.5-5000 fmol). 3. NTS microinjection of 5 fmol ANGII elicited a transient (28.2 +/- 6 s; mean +/- s.e.m.) bradycardia (-18 +/- 3 beats min-1), and decreased phrenic nerve activity cycle length and amplitude (P < 0.05). At higher doses of ANGII a similar respiratory response was seen but heart rate changes were inconsistent. 4. The baroreceptor reflex bradycardia was depressed significantly by NTS microinjections of ANGII (5-5000 fmol) in a dose-dependent manner with the reflex gain decreasing from 1.7 +/- 0.16 to 0.66 +/- 0.1 beats min-1 mmHg-1 (P < 0.01) at 5000 fmol. Although the chemoreceptor reflex bradycardia was depressed at a low dose of ANGII (5 fmol), all higher doses (50-5000 fmol) produced a dose-dependent potentiation of the reflex bradycardia (maximally +64 +/- 8 %). The respiratory component was unaffected. The effects of ANGII on both reflexes were blocked by an ANGII type 1 (AT1) receptor antagonist, losartan (20 microM). 5. The potentiating action of ANGII on the chemoreceptor reflex cardiac response was abolished by a neurokinin type 1 (NK1) receptor blocker (CP-99,994, 5 microM) but this had no effect on the baroreceptor reflex. 6. AT1 receptors in the NTS can depress the baroreceptor reflex bradycardia which is independent of NK1 receptors. The ANGII effect on the cardiac component of the chemoreceptor reflex is bi-directional being inhibited at low concentrations and potentiated at higher concentrations; the latter involves NK1 receptors and presumably results from release of substance P.
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PMID:Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii - a microinjection study in the rat. 1056 46


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