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)

Exogenous administration of lipoxin A4 (LXA4) to guinea pig isolated bronchus produced contractile effects in a concentration-dependent manner (1, 3, and 6 microM). These responses were potentiated when preparations were previously incubated with thiorphan (10 microM), an inhibitor of tachykinin breakdown, but were significantly depressed when sensory nerves were previously desensitized in vitro by capsaicin (10 microM for 15 min) challenge. Ruthenium red (10 microM for 20 min), a blocker of the cationic channel coupled to the capsaicin receptor, also produced, although in a weaker manner, a reduction in bronchomotor responses elicited by LXA4. On the other hand, preexposure to omega-conotoxin (0.1 microM for 45 min), a blocker of neuronal voltage-dependent Ca2+ channels, did not modify the LXA4 contractile effects. Furthermore, LXA4 (6 microM) superfusion of guinea pig bronchial tissue elicited a significant calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) release that was reduced by capsaicin (10 microM, 30 min) desensitization. Finally, LXA4 (10 microM) was unable to displace [3H]resiniferatoxin binding in dorsal root ganglion of rat and guinea pig. These findings support (1) a role for LXA4 in activating motor sensory function of capsaicin-sensitive nerves; (2) this activation mechanism is marginally ruthenium red-sensitive and omega-conotoxin-resistant; and (3) the interaction does not involve the recognized binding site on the vanilloid receptor. As a whole this study presents LXA4 as an endogenous mediator activating sensory nerves potentially involved in basic mechanisms of airway diseases.
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PMID:Pharmacologic and neurochemical evidence for the activation of capsaicin-sensitive sensory nerves by lipoxin A4 in guinea pig bronchus. 138 7

1. The effect of systemic administration of ruthenium red on bronchospasm induced by acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [beta Ala8]-neurokinin A (NKA)-(4-10) for NK-1 and NK-2 receptors, respectively) was studied in anaesthetized guinea-pigs. 2. The bronchospasm induced by capsaicin was reduced by ruthenium red, which did not affect the response induced by acetylcholine. Atropine, which totally blocked the response to acetylcholine, also partially blocked the bronchospasm induced by capsaicin. 3. The inhibitory action of atropine and ruthenium red on the bronchospasm produced by capsaicin was additive, independently from the order of administration of the two antagonists. 4. Ruthenium red induced an increase in [Sar9]SP sulfone-bronchospasm and a marked enhancement of the bronchomotor response to [beta Ala8]NKA-(4-10). This latter was antagonized by the prior administration of the selective NK-2 receptor antagonist MEN 10,376. 5. Pretreatment with guanethidine or propranolol increased the airway constriction induced by [beta Ala8]NKA-(4-10). Furthermore, pretreatment with guanethidine prevented the enhancement induced by ruthenium red, showing that activation of NK-2 receptors influences the sympathetic bronchodilator drive to the airways. 6. It is concluded that ruthenium red antagonizes selectively the in vivo excitatory effect of capsaicin in guinea-pig airways. Furthermore, the additivity of the blocking action of ruthenium red and atropine indicates that two distinct mechanisms take place in bronchospastic response to i.v. capsaicin in this species.
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PMID:Effect of ruthenium red on the bronchoconstriction induced by capsaicin and by selective tachykinin receptor agonists in anaesthetized guinea-pig. 138 38

1. In the presence of atropine and guanethidine (3 mumol/l each), electrical field stimulation (1-20 Hz) produced frequency-dependent relaxations of the histamine- (3 mumol/l) induced vascular tone in isolated rings from the guinea-pig pulmonary artery. The electrically-evoked relaxations were abolished by tetrodotoxin (1 mumol/l). The amplitude of these nerve-mediated, non-adrenergic non-cholinergic (NANC) relaxations was unaffected by removal of the vascular endothelium produced through rubbing of the internal surface. 2. Capsaicin (1 mumol/l) produced a prompt and sustained relaxation of the histamine-induced tone which was unaffected by removal of the endothelium. A second application of capsaicin 60-120 min later had no further relaxant effect, indicating desensitization. After in vitro capsaicin desensitization, the electrically-evoked NANC relaxations were abolished, both in the presence or absence of the vascular endothelium. 3. Substance P evoked a prompt and transient relaxation in precontracted arterial rings with intact endothelium and a transient small contraction in rings in which the endothelium had been mechanically removed. The selective NK-1 receptor agonist, [Pro9]-substance P sulfone closely mimicked the relaxation produced by substance P while the selective NK-2 or NK-3 receptor agonists had no relaxant effect. Tachyphylaxis to substance P did not modify the amplitude of the capsaicin-induced relaxation. 4. Human alpha calcitonin gene-related peptide (CGRP) produced a prompt and sustained relaxation both in the presence and absence of the vascular endothelium. 5. Ruthenium red (10 mumol/l) blocked the relaxation to capsaicin while leaving unaffected the relaxation to electrical field stimulation or CGRP (0.1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sensory nerves, vascular endothelium and neurogenic relaxation of the guinea-pig isolated pulmonary artery. 169 64

1. In the present study, the levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) in human cardiopulmonary tissue were determined in combination with studies on CGRP-LI release from the left anterior descending coronary artery (LAD) and functional effects of CGRP on coronary arterial tone. 2. The highest levels of CGRP-LI were found in the LAD followed in declining order by the bronchus, right atrium, pulmonary artery, lung and left ventricle. 3. Exposure to capsaicin evoked a clear-cut increase in CGRP-LI outflow, suggesting release from isolated large specimen of the LAD. This release was Ca2(+)-dependent and was markedly attenuated by incubation with the mitochondrial Ca2(+)-inhibitor, ruthenium red. Exposure to potassium also released CGRP-LI in a Ca2(+)-dependent fashion from the LAD. 4. In functional experiments on human epicardial coronary arteries with an inner diameter of 0.4 to 0.8 mm, human CGRP alpha and beta relaxed the potassium-precontracted arteries equipotently. Substance P (SP) also relaxed these precontracted arteries but the relaxation could be prevented by incubation with methylene blue, an inhibitor of endothelium derived relaxing factor (EDRF)-mechanisms, which did not influence the effect of CGRP. 5. Capsaicin evoked a ruthenium red-sensitive relaxation of the potassium-precontracted arteries. However, ruthenium red did not affect the relaxations induced by CGRP or SP. Furthermore, the capsaicin effect was not influenced by methylene blue. 6. It is concluded that CGRP-LI is present in human cardiopulmonary tissue and can be released upon exposure to high concentrations of capsaicin as well as potassium. CGRP causes relaxation of arteries independently of EDRF activation and closely resembles the vasodilator effects of capsaicin. This supports the view that the coronary vasodilatation observed upon sensory nerve activation is mediated by CGRP. Ruthenium red inhibits capsaicin-induced CGRP-LI release and functional effects and may thus serve as an experimental tool in evaluating the function of capsaicin-evoked stimulation of peripheral nerve terminals.
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PMID:Calcitonin gene-related peptide and human epicardial coronary arteries: presence, release and vasodilator effects. 170 13

The effects of Ruthenium red and its antagonism of capsaicin-induced action on the electrophysiological behavior of myenteric neurons were investigated with intracellular recording techniques in the isolated guinea-pig ileum. Ruthenium red antagonized dose-dependently (1-10 microM) a capsaicin-induced marked long-lasting slow depolarizing action associated with increased input resistance, during which the cells spiked repeatedly or displayed anodal break excitation. This action of capsaicin has been found to be mediated via a release of substance P from sensory nerve endings. The slow depolarizing response to exogenous substance P applied by pressure microejection, which mimicked the capsaicin-induced action, was not affected by Ruthenium red. Therefore, present results indicate that Ruthenium red antagonizes the specific effect of capsaicin on myenteric neurons by acting on the presynaptically located peripheral nerve terminals of sensory neurons and inhibiting the release of substance P. Electron-microscopic examination showed that the neurotoxic action of capsaicin towards extrinsic sensory nerve fibers was also dose-dependently (1-10 microM) protected by pretreatment of ruthenium red. Present results suggest that Ruthenium red inhibits a capsaicin-induced activation of cation channels at the cell membrane of sensory nerves.
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PMID:Ruthenium red antagonism of the effects of capsaicin mediated by extrinsic sensory nerves on myenteric plexus neurons of the isolated guinea-pig ileum. 171 8

1. We have investigated the ability of prostacyclin (PGI2) to contract guinea-pig isolated bronchi and the possible involvement of capsaicin-sensitive primary afferents in the response to PGI2. 2. PGI2 (0.1-100 microM) produced concentration-dependent contractions of the guinea-pig isolated bronchi. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced the PGI2-induced contraction at all concentrations tested. A capsaicin-resistant component of contraction (40-60% of the overall response) was also evident. 3. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PGI2-induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine. 4. MEN 10, 207, (Tyr5, D-Trp6,8,9, Arg10)-neurokinin A (4-10) (3 microM), a selective antagonist of NK2-tachykinin receptors, significantly decreased PGI2-induced contractions and neurokinin A-induced contractions, without affecting the response to acetylcholine. 5. The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6. These results indicate that PGI2-induced contraction of the guinea-pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin-sensitive primary afferents. In as much as PGI2-activation of primary afferents is sensitive to ruthenium red, we suggest that PGI2 shares a common mechanism of tachykinin release with that activated by capsaicin.
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PMID:Prostacyclin activates tachykinin release from capsaicin-sensitive afferents in guinea-pig bronchi through a ruthenium red-sensitive pathway. 172 16

The effects of ruthenium red, an inorganic dye with known capsaicin antagonist properties, was investigated in the rabbit eye. At a dose of 0.24 nmol ruthenium red inhibited the inflammatory effects of capsaicin (1 or 8 nmol). Unexpectedly, when the dye was injected in doses ranging from 0.24 to 7.4 nmol, it caused an inflammatory response with constriction of the pupil (miosis) and a breakdown of the blood-aqueous barrier, leading to a rise intraocular pressure. Tetrodotoxin (30 nmol) inhibited the ruthenium red-induced rise in intraocular pressure but had less effect on the miotic response. The tachykinin antagonist spantide inhibited the miosis but had no effect on the rise in intraocular pressure. Ruthenium red induced an increase in substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity in the aqueous humor. These levels were positively correlated with the rise in aqueous humor protein concentration. The ruthenium red-induced miosis and, to a less extent, the rise in intraocular pressure were inhibited by the Ca2+ channel-blocking agent omega-conotoxin GVIA (CTX), indicating a partial dependence on an influx of extracellular Ca2+. CTX also attenuated the miotic effect of capsaicin but had no effect on the capsaicin-induced rise in intraocular pressure. It is concluded that, in the rabbit eye, ruthenium red induces a neurogenic inflammatory response besides its capsaicin antagonist effects.
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PMID:Ruthenium red and capsaicin induce a neurogenic inflammatory response in the rabbit eye: effects of omega-conotoxin GVIA and tetrodotoxin. 172 55

Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 microM) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20-30 min. Repeated applications of 3 microM capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i.e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as "non-responders", 3 microM capsaicin did not elicit a secretory response. No desensitization of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response. Tetrodotoxin (100 nM), hexamethonium (10 microM), and yohimbine (50 microM) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 microM) abolished the secretory response to 3 microM capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 microM substance P (SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 microM capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues.
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PMID:The effects of capsaicin upon electrogenic ion transport in rat descending colon. 172 6

Different modes by which Ca2+, entering the nerve terminal, promotes transmitter secretion as well as the ability of protons to release neuropeptides, have been shown in peripheral endings of capsaicin-sensitive afferents. We have studied these two aspects in the central endings of these neurons by measuring the release of calcitonin-gene related peptide-like immunoreactivity (CGRP-LI) from slices of the dorsal half of the guinea pig spinal cord. Although capsaicin (1 microM) released both CGRP-LI and substance P-like immunoreactivity (SP-LI), CGRP-LI was chosen as the sole suitable marker of peptides released from central terminals of capsaicin-sensitive afferents, since after in vitro desensitization to capsaicin (1 microM capsaicin for 20 min), high K+ (80 mM) failed to evoke CGRP-LI release, whereas SP-LI release was still observed. The capsaicin (1 microM)-evoked CGRP-LI release was entirely dependent on extracellular Ca2+. It was unaffected by 0.3 microM tetrodotoxin (TTX), slightly reduced by 0.1 microM omega-conotoxin (CTX) and blocked by 10 microM Ruthenium red (RR). The Ca(2+)-dependent K+ (80 mM)-evoked CGRP-LI release was unaffected by TTX, markedly reduced by CTX and only moderately inhibited by RR. Low pH (pH 5) produced a remarkable increase in CGRP-LI outflow that was abolished after exposure to capsaicin, reduced by about 50% in Ca(2+)-free medium and unaffected by TTX (0.3 microM). The Ca(2+)-dependent component of the proton-evoked CGRP-LI release was abolished in the presence of RR (10 microM) and slightly inhibited by CTX (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different pathways by which extracellular Ca2+ promotes calcitonin gene-related peptide release from central terminals of capsaicin-sensitive afferents of guinea pigs: effect of capsaicin, high K+ and low pH media. 172 64

In the rat isolated urinary bladder, exposure to capsaicin (1 microM) produced a contraction thought to involve neuropeptide(s) release from sensory nerves. A second application of the drug had no motor effect indicating desensitization. The establishment of the desensitized state requires the presence of extracellular calcium. In the presence of Ruthenium red 9RR, 30 nM-10 microM) the first response to capsaicin was reduced and a concentration-dependent protection from capsaicin desensitization was observed. RR up to 10 microM had no inhibitory effect toward contractions produced by exogenous substance P nor by electrical stimulation of efferent nerves.
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PMID:Protective action of ruthenium red toward capsaicin desensitization of sensory fibers. 245 37


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