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)

Transmural electrical stimulation and nicotine produced a relaxation of dog cerebral artery strips denuded of endothelium, which was abolished by tetrodotoxin and hexamethonium, respectively, and also suppressed by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor. The inhibition was reversed by L-arginine but not by the D-enantiomer. L-NA also suppressed the endothelium-dependent relaxation by substance P but not the response to NO and nitroglycerin. Treatment with high concentrations of nitroglycerin or sodium nitroprusside markedly inhibited the relaxant response to nicotine, substance P and NO but not the response to papaverine. Slight, slowly developing relaxations caused by L-arginine in the endothelium-denuded arteries were not potentiated by repeated applications of the amino acid or by exposure of the strips for 24 hr to the bathing medium. Ca++ ionophore-induced contractions in the denuded strips were not potentiated by L-NA. Nicotine significantly increased the level of cyclic GMP in the arteries without endothelium; the increment was abolished by treatment with L-NA and hexamethonium. NO does not seem to be synthesized in smooth muscle in an amount sufficient to produce significant relaxation. It may be concluded that NO liberated from vasodilator nerves activates guanylate cyclase in smooth muscle and produces cyclic GMP, resulting in cerebroarterial relaxation.
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PMID:Role of nitric oxide in neurally induced cerebroarterial relaxation. 165 33

1. Contractile responses and acetylcholine release evoked by nicotine in guinea-pig detrusor strips were determined by isotonic transducer and radioimmunoassay, respectively. Nicotine stimulated acetylcholine release and a contractile response in guinea-pig detrusor strips treated with the cholinesterase inhibitor, methanesulphonyl fluoride (MSF). Both actions evoked by nicotine were antagonized by the nicotinic receptor antagonist, hexamethonium but were insensitive to tetrodotoxin. 2. A sympathetic nerve blocker, guanethidine and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. The inhibitory effects of guanethidine and rpwwL-SP on acetylcholine release were significantly greater than corresponding effects on the contraction evoked by nicotine. 3. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine. Conversely, after treatment with guanethidine to block release of a mediator from sympathetic nerve endings, nicotine-induced responses were not affected by rpwwL-SP. 4. Nicotine-induced contraction was reduced to 30% by the muscarinic cholinoceptor antagonist, atropine and completely abolished after desensitization of P2-purinoceptors with alpha,beta-methylene ATP in the presence of atropine. 5. A concentration-contractile response curve to neurokinin A (NKA) was shifted to the left after cholinesterase inhibition with MSF. Atropine abolished the facilitatory effect of MSF and partially inhibited contractions induced by NKA at 100 nM to 1 microM. The contractile responses to substance P methyl ester (SPOMe) and Tyr0-neurokinin B (Tyr0-NKB) were not influenced by MSF or atropine. 6. After desensitization of NK, tachykinin receptors with SPOMe or preincubation with senktide, the cholinergic component of the nicotine-induced contraction was the same as the control value (100%). 7. Our findings give further support to our previous results: nicotine stimulates acetylcholine release in a tetrodotoxin-resistant manner in guinea-pig bladder and acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinin(s). It is suggested that the tachykinin receptor subtype involved in acetylcholine release is NK,.
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PMID:Contrasting effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder [corrected]. 171 27

1. Nicotine-induced contraction of bronchial preparations isolated from 3, 6, 10, 50 and 100 week old guinea-pigs were studied. 2. Contractile responses to nicotine were inhibited by hexamethonium and a substance P antagonist but not by atropine or tetrodotoxin, suggesting that the nicotine-contraction was mediated through a release of substance P-like material(s). 3. The pD2 value (potency) of nicotine did not change with age from 3 to 10 weeks but decreased thereafter to 100 weeks, while no age-related change was found in the pD2 value of substance P. The pA2 value of hexamethonium did not change with age, suggesting that the affinity of drugs to nicotine receptors does not change with age. 4. These results suggest that possibility that age-related change in the pD2 value of nicotine is due to a change in the amount of nicotine receptors but not to a change in the affinity of nicotine to its receptors.
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PMID:Effect of ageing on nicotine-induced contraction of guinea-pig bronchial preparation. 234 Oct 16

Nicotine-induced contraction of the isolated guinea pig bronchial preparation was abolished by capsaicin and a substance P (SP) antagonist [( D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP). Nicotine increased the release of immunoreactive SP from the preparations. The nicotine-evoked release of immunoreactive SP from the bronchial preparation was reduced by hexamethonium but not by tetrodotoxin. The results indicate that the responses to nicotine of the guinea pig bronchial preparation were mediated through the release of SP-like material(s), and that the nicotine-induced response may be produced through a process independent of the sodium action potential. In conclusion, the most likely site of action of nicotine in the isolated guinea pig bronchial preparation is the nicotinic receptor of SP immunoreactive nerves.
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PMID:Possible involvement of substance P immunoreactive nerves in the mediation of nicotine-induced contractile responses in isolated guinea pig bronchus. 241 45

1. A possible role of substance P-containing nerves in the contractile response to nicotine was investigated in isolated rabbit bronchial smooth muscle preparation. 2. Nicotine caused a contraction which was attributed to the release of acetylcholine in the rabbit bronchus. The response was reduced by capsaicin (10(-5) M) and a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7.9, Leu11] substance P (10(-5) M). 3. Substance P (10(-7) M)-induced contraction was reduced by atropine (10(-6) M) and potentiated by physostigmine (10(-6) M). Furthermore, substance P (10-7 M) enhanced the release of tritium or acetylcholine from the [3H]choline labelled bronchi. 4. Results suggest that substance P-like tachykinin accelerates the nicotine-evoked prejunctional endogenous neural release of acetylcholine on the nervous cells in the rabbit bronchial preparation.
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PMID:Substance P-containing nerves mediate nicotine-induced contractions of rabbit bronchial smooth muscle. 245 Aug 7

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in dogs in vivo. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time due to particle rotation (relaxation), which is thought to be inversely related to CM of AM (J. Appl. Physiol. 55: 1196-1202, 1983). The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to base-line values within 15 min. With the inhalation of the smoke of up to five cigarettes, peak lambda 0 was increased; with a further increase in the number of cigarettes, the effect of cigarette smoke decreased or disappeared. Nicotine injection and acetylcholine inhalation increased respiratory resistance to a degree similar to that observed with cigarette smoke but did not change lambda 0. However, either substance P (SP) or capsaicin injection increased lambda 0 in a fashion similar to that noted with cigarette smoke inhalation. Repeated administration of SP produced a significant tachyphylaxis of the effect, and capsaicin did not increase lambda 0 after the cigarette smoke-induced tachyphylaxis of the effect. Colchicine inhibited the cigarette smoke-induced increase in lambda 0. These results suggest that cigarette smoke increases CM of AM, probably through the release of tachykinins including SP from sensory nerves in the lung.
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PMID:Acute effect of cigarette smoke on cytoplasmic motility of alveolar macrophages in dogs. 246 40

The release of previously incorporated [3H]serotonin and its presynaptic modulation were studied in slices of rabbit superior colliculus. Electrical stimulation at frequencies of 0.017-3 Hz greatly increased the outflow of tritiated compounds; this response was almost abolished by tetrodotoxin and in a low calcium medium. Unlabelled serotonin, when added in the presence of nitroquipazine, an inhibitor of high-affinity neuronal serotonin uptake, reduced the electrically evoked overflow of tritium, an effect antagonized by metitepin. Given alone, metitepin caused an increase. The evoked overflow was also decreased by clonidine, and the effect of clonidine was counteracted by phentolamine. Phentolamine itself increased the overflow response. However, this was probably not due to antagonism against an inhibitory effect of endogenous noradrenaline because, first, the selective alpha 2-adrenoceptor antagonist idazoxan did not share with phentolamine the overflow-enhancing effect, second, phentolamine continued to increase the overflow after noradrenergic axons had been destroyed by 6-hydroxydopamine, and third, the facilitatory effects of metitepin and phentolamine were not additive. Phentolamine, like metitepin, antagonized the presynaptic inhibitory effect of serotonin, indicating that it may increase the evoked overflow of tritium by blocking serotonin receptors rather than alpha-adrenoceptors. Ethylketocyclazocine decrease the electrically evoked overflow, and its effect was prevented by naloxone: peptides selective for opioid mu- or delta-receptors caused no change. Nicotine increased the basal outflow of tritium (in the absence of electrical stimulation); the increase was attenuated by hexamethonium and low calcium medium. No or minimal changes in tritium outflow were obtained with beta-adrenoceptor, dopamine receptor, muscarine receptor and GABA receptor ligands or with substance P and glutamate. In conjunction with our previous studies, these results indicate that serotonin is a neurotransmitter in the superior colliculus. Its release is modulated through presynaptic autoreceptors (probably 5-HT1), alpha 2-adrenoceptors, opioid kappa-receptors and nicotine receptors, of which only the autoreceptors receive an endogenous input, at least under the experimental conditions chosen. Each of the three groups of collicular monoamine axons that we have studied recently (cholinergic, noradrenergic, serotoninergic) possesses a specific pattern of presynaptic, release-modulating receptors. A physiological role seems likely only for the alpha 2-autoreceptors at the noradrenergic and the 5-HT1-autoreceptors at the serotoninergic axons.
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PMID:Release and modulation of release of serotonin in rabbit superior colliculus. 255 33

1. The neurotransmitter of the non-cholinergic excitatory nerves in the rainbow trout stomach was identified on the basis of the pharmacological properties of the contractile responses to transmural stimulation (TMS) and nicotine. 2. TMS caused tetrodotoxin-sensitive contractions of rainbow trout stomach strips in a frequency-dependent manner (0.5-50 Hz). Atropine (1 microM) significantly decreased the contractile response to low-frequency stimulation (0.5-2 Hz), but did not affect that to high-frequency stimulation (3-20 Hz). 3. The atropine-resistant contractile response to TMS (20 Hz) was unaffected by hexamethonium (100 microM), phentolamine (5.4 microM), pyrilamine (1 microM), naloxone (1 microM) or substance P-induced desensitization. 4. 5-Hydroxytryptamine (5-HT, 3 nM-3 microM) caused atropine-resistant contractions in a concentration-dependent manner. In the presence of atropine, methysergide (1 microM) decreased the contractile responses to TMS and 5-HT. 5. Nicotine (3 microM-500 microM) induced atropine-resistant contractions that were completely abolished by tetrodotoxin or hexamethonium. Also methysergide inhibited the contractile responses to nicotine. 6. An acid extract of rainbow trout stomach exhibited atropine-resistant contractions that were decreased by methysergide, in both rainbow trout stomach and guinea-pig ileum longitudinal smooth muscle preparations. 7. The present results indicate that, in longitudinal muscle strips of the rainbow trout stomach, 5-HT is one of the mediators (neurotransmitters) of the non-cholinergic excitatory contractions induced by TMS and nicotine.
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PMID:5-Hydroxytryptamine is a possible neurotransmitter of the non-cholinergic excitatory nerves in the longitudinal muscle of rainbow trout stomach (Salmo gairdneri). 257 65

The cholinoceptive properties of dorsal horn neurons (lamina III-V) were investigated by means of intracellular recordings from the rat isolated spinal cord slice preparation. In half of the neurons investigated, acetylcholine (ACh) evoked a dose-dependent slow depolarization and increase in excitability; hyperpolarization was observed in 10% of neurons. Acetyl-beta-methylcholine (MCh) similarly depolarized 39% and hyperpolarized 25% of neurons tested; depolarization was also observed following bethanechol. Responses to the muscarinic agonists were abolished by atropine (10(-5) M). Nicotine depolarized 84% of tested neurons; dihydro-beta-erythroidine (5 x 10(-5) M) and (+)-tubocurarine (10(-6) M) antagonized this depolarization. ACh-, MCh- and nicotine-induced depolarizations, associated with changes in input resistance, were maintained in the presence of tetrodotoxin (10(-6) M). Substance P, as well as repetitive electrical stimulation of the dorsal root, also evoked depolarization in ACh-sensitive neurons. Atropine, but not (+)-tubocurarine, diminished responses to both substance P and dorsal root stimulation. These results indicate that dorsal horn neurons are ACh-sensitive and possess both muscarinic and nicotinic receptors. In addition, the parallel sensitivity of neurons to muscarinic agonists, substance P and dorsal root stimulation, as well as the parallel antagonistic effect of atropine, are supportive of a common ionic mechanism underlying the activation of muscarinic and substance P receptors.
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PMID:Cholinergic effects on spinal dorsal horn neurons in vitro: an intracellular study. 260 85

Neural pathways involved in cough and reflex bronchoconstriction and the effects of drugs on these airway reflexes have been studied in unanaesthetised guinea-pigs exposed to aerosols of citric acid (0.13-0.78 M), capsaicin (30 microM), nicotine (9.2 mM) and histamine (0.9 mM). The number of coughs was counted during the first 3 min of exposure and the time to onset of signs of dyspnea, as an indication of bronchoconstriction, was measured. Citric acid produced bronchoconstriction and dose-dependently increased the number of coughs. Capsaicin produced both cough and bronchoconstriction. Nicotine mainly produced cough and histamine bronchoconstriction. Pretreatment of adult guinea-pigs with capsaicin (50 mg kg-1 s.c.) produced a long-lasting (greater than or equal to 10 weeks) depletion of substance P- and calcitonin gene related peptide-like immunoreactivities in the sensory nerves of the larynx, tracheobronchial tree and lung. In capsaicin-treated animals, citric acid (0.39 M) and capsaicin (30 microM) caused neither cough nor bronchoconstriction. Nicotine (9.2 mM) and mechanical stimulation still produced cough, and histamine (0.9 mM) bronchoconstriction. It is concluded that in guinea-pigs both capsaicin-sensitive (probably C-fibre endings) and capsaicin-resistant (probably rapidly adapting stretch receptors) afferent neurons may be involved in cough and reflex bronchoconstriction.
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PMID:Cough and bronchoconstriction mediated by capsaicin-sensitive sensory neurons in the guinea-pig. 298 Feb 86


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