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)

Intrathecal administration of substance P at the lower thoracic spinal level has an antinociceptive effect on reaction time in the tail-flick test; this response is blocked by naloxone i.v. but not by i.v. administration of opiate antagonists which do not cross the blood-brain barrier. As morphine-induced analgesia is blocked by adenosine antagonists, to determine whether this substance P-induced, opioid-mediated antinociception also includes a purine link, the adenosine receptor antagonist, caffeine, was given systemically 10 min prior to substance P administration. In control rats pretreated with saline, substance P (6.5 nmol) produced an increase in reaction time to about 160% of preadministration values at one min after intrathecal injection. The effect could also be observed at 6 min after this injection. Pretreatment with 16 or with 32 mg/kg of caffeine i.p. blocked the response to substance P, and produced a hyperalgesia similar to that reported in studies at the lumbo-sacral spinal level. These results indicate that the adrenal opioid-induced antinociception observed upon intrathecal administration of substance P at the lower thoracic level occurs via an adenosine link. This is the first demonstration of a purine link in the expression of antinociceptive effects of an endogenously released opioid.
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PMID:Adenosine receptor link in an adrenal opioid-induced antinociception in the rat tail-flick test. 137 72

The effect of temperature on the substance P-induced contraction of the isolated tracheal strip-chain preparation from the golden hamster has been examined. A decrease of bath temperature from 37 to 20 degrees C augmented the contractile response of the trachea caused by substance P. Similar cooling-induced augmentation was observed in the contractile responses to caffeine and carbachol, but not to potassium chloride. The increased responsiveness with lowered temperature of the trachea to substance P may be due to the acceleration of Ca2+ release from an intracellular storage site.
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PMID:Cooling-induced augmentation of the contractile response of the golden hamster tracheal muscle to substance P in-vitro. 242 77

The present investigation was prompted by previous studies in our laboratory which have indicated that tachykinins enhance depressant effects of purines and that the purine adenosine mediates a vibration-induced depression of nociceptive dorsal horn neurons. Extracellular recordings were made from single nociceptive neurons in the lower lumbar segments of anaesthetized cats. Vibration (80 Hz; 2.5-3.5 s every 20-25 s) was applied to the hindlimb using a feedback-controlled mechanical stimulator. The tachykinins physalaemin, substance P and neurokinin A were administered by iontophoresis. Physalaemin was tested on vibration-induced responses of 29 neurons; each neuron was excited by this tachykinin. To control for possible changes in the response to vibration caused by the excitation per se, statistical comparisons were made of the vibration-induced responses during excitation by tachykinins and during excitation by glutamate. In 16 cases the magnitude of the vibration-induced depression was significantly greater during the excitation caused by physalaemin. With the remaining neurons the response to vibration failed to differ during the excitation by physalaemin compared with the excitation by glutamate. In four of the 16 cases subthreshold applications of vibration caused depression after administration of physalaemin. The P1-purinergic (adenosine) antagonist, caffeine, was administered in three cases where vibration caused depression only with application of physalaemin. In each of these cases the depression was reversibly blocked by caffeine (10 or 40 mg kg-1 i.v.). The magnitude of vibration-induced depression was significantly increased during excitation by neurokinin A (5/14 neurons) or by substance P (1/9 neurons). From the results of the present study we suggest that tachykinins enhance the vibration-induced depression. This enhancement may be due to enhanced depression by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tachykinins enhance the depression of spinal nociceptive neurons caused by cutaneously applied vibration in the cat. 246 89

The action of substance P (SP) on a rat pancreatic acinar cell line, AR4-2J, was examined using the whole-cell voltage-clamp technique. Pressure application of SP evoked inward currents accompanying increased membrane conductance. The SP-induced response was suppressed in Ca2+-free or low-Na+ solution. Treatment of cells with caffeine or A23187 produced a transient inward current and depressed the response to SP. Intracellular application of inositol 1,4,5-trisphosphate or guanosine 5'-O-(3-thiotriphosphate) elicited sustained inward currents and suppressed the SP-induced response. The results suggest that activation of SP receptors stimulates the formation of inositol phosphates via a guanine nucleotide-binding protein and leads to the rise in intracellular Ca2+, thereby activating a cation conductance in AR4-2J cells.
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PMID:Inositol trisphosphate-linked calcium mobilization couples substance P receptors to conductance increase in a rat pancreatic acinar cell line. 246 8

The effect of extracellular calcium on the release of calcitonin gene-related peptide (CGRP) induced by electrical field stimulation from enteric nerves of isolated rat ileum was studied; the effect of high potassium, veratridine and caffeine was also examined. Release of endogenous substance P from enteric nerves was also measured for comparison. Electrical field stimulation (10 Hz, 0.3 ms for 2 min) of the ileum preparation caused a significant (P less than 0.001) increase in the release of CGRP and substance P from enteric nerves. The evoked, but not the basal, release of both CGRP and substance P was inhibited in the presence of tetrodotoxin (TTX). The release of CGRP and substance P induced by electrical stimulation was abolished in Ca2+-free medium containing CDTA and also in normal medium containing the calcium channel blocker cadmium chloride (CdCl2), with no change in the level of the basal release of both peptides. However, potassium depolarization (76 and 110 mM) failed to evoke an increase in the release of endogenous CGRP, although it did cause an increase in the release can be induced by mobilization of calcium from intracellular Ca2+ stores. Veratridine, on the other hand, did not cause an increase in CGRP release, although substance P and VIP release was induced by veratridine from the same preparations. The results of the present study have demonstrated that CGRP release from enteric nerves requires the presence of extracellular calcium but, unlike substance P and most other transmitters reported to show calcium-dependent release, potassium depolarization does not induce CGRP release from enteric nerves of rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of calcitonin gene-related peptide from rat enteric nerves is Ca2+-dependent but is not induced by K+ depolarization. 246 7

1. KCl, carbachol, neurokinin A and endothelin produced concentration-dependent contractions of mucosa-free muscle strips from the dome of the human urinary bladder. The maximal response to carbachol or neurokinin A exceeded that to KCl, while the maximal response to endothelin approached that to KCl. 2. Nifedipine (1 microM) abolished the response to KCl, reduced the response to carbachol or neurokinin A but had no effect on the response to endothelin. Bay K 8644 (1 microM) markedly potentiated the response to KCl but had little or no effect on the response produced by the other stimulants. 3. Superfusion of the strips with a nominally calcium (Ca)-free medium containing EDTA (1 mM) for 30 min markedly reduced the response to carbachol, neurokinin A and endothelin, although a small response was still evident at high concentrations. Likewise, after a prolonged (60 min) superfusion of the strips with a high K (80 mM) Ca-free medium plus EDTA (1 mM) these three agonists still produced a small contractile response. 4. The nifedipine (1 microM) resistant response to carbachol, neurokinin A or endothelin was markedly depressed by LaCl3 (1 mM). In contrast, the nifedipine-(1 microM) resistant response to carbachol was not modified by NiCl2 (0.1 mM) or omega-conotoxin (0.1 microM). 5. Caffeine produced divergent effects depending upon the temperature of incubation: a relaxation at 37 degrees C and a concentration-dependent (2.5-20 mM) contraction at 25 degrees C. The latter was markedly inhibited by procaine (3 mM) but unaffected by nifedipine (1 microM). 6. After a prolonged (60 min) superfusion with a high K, Ca-free medium containing EDTA the response to carbachol (100 microM) was abolished by previous exposure to procaine (3 mM). Conversely, the response to endothelin (1 microM) was unaffected by procaine. The response to endothelin in these experimental conditions was also resistant to LaCl3 (1 mM). 7. These findings indicate that multiple sources of Ca are mobilized for contraction of the human bladder muscle by different stimulants. Dihydropyridine- and voltage-sensitive Ca channels provide the major if not the sole source of Ca for the response to KCl, play some role in the response to muscarinic (carbachol) or NK-2 tachykinin receptor stimulation but are not involved in the response to endothelin. Carbachol, neurokinin A and endothelin all mobilize a Ca pool (either extracellular or located at membrane level) which is LaCl3-sensitive but nifedipine-resistant. Neither T- nor N-type channels appear to be involved in the response to carbachol. In addition, these agents mobilize a tightly bound Ca pool independently from membrane depolarization. This latter pool is probably a procaine-sensitive intracellular source of activator Ca mobilized by caffeine and carbachol. The failure of procaine to prevent the response to endothelin in high K, Ca-free medium raises the possibility that this peptide mobilizes an intracellular source of activator Ca, distinct from the caffeine- and carbachol-sensitive pool.
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PMID:Multiple sources of calcium for contraction of the human urinary bladder muscle. 248 Jan 67

The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. Active phorbol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.
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PMID:Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. 248 99

1. An enzyme which can be extracted from brain inactivates nerveside in the optimum pH range 5.8-7.0.2. The polybasic acids trypan blue and its analogue trypan red, bromphenol blue and its analogue bromthymol blue at concentrations of 0.22 mM and ethylenediaminetetra-acetic acid (EDTA) at a concentration of 1 mM are strong inhibitors of the enzyme.3. Penicillin which is a monobasic carboxylic acid also inhibits the enzyme but only if concentrations as high as 3.6 mM are used. The antibiotic streptomycin which is a basic substance does not inhibit the enzyme.4. Caffeine at a concentration of 7.2 mM only weakly inhibits the enzyme.5. Chymotrypsin and wheat germ acid phosphatase also inactivate nerveside at pH 5.9 and are inhibited by the acidic dyes and penicillin. EDTA inhibits wheat germ phosphatase but activates chymotrypsin.6. Inactivation of nerveside by the brain enzyme and by wheat germ phosphatase is different from the action of chymotrypsin. Nerveside solutions incubated with chymotrypsin completely lose all biological activity whereas if incubation is carried out with either the brain enzyme or wheat germ acid phosphatase a residual biological activity remains even when the concentration of these two enzymes is increased. This residual biological activity is due to a peptide as it is destroyed by chymotrypsin.7. The manner in which nerveside is inactivated by the brain enzyme is uncertain as the preparation of the latter contained phosphodiesterase and protease activities which were similarly inhibited by the acid dyes, penicillin and EDTA.8. Pentylenetetrazole, picrotoxin, strychnine and tetanus toxin do not inhibit the brain enzyme.9. The nerveside-inactivating enzyme is not identical with the Substance P-inactivating enzyme in brain as the former is inhibited by EDTA while the latter is not.
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PMID:The inhibitory effect of convulsant agents on the enzyme in brain which inactivates nerveside. 439 Mar 85

Intracellular recordings were made from myenteric neurons of the guinea-pig ileum in vitro; they were classified into S and AH neurons according to electrophysiological criteria. ATP (10 nM-100 microM) inhibited excitatory synaptic potentials in the myenteric plexus; fast excitatory postsynaptic potentials and slow excitatory postsynaptic potentials of S neurons and slow excitatory postsynaptic potentials in AH neurons. This inhibitory action was reversible and dose-dependent, and was usually followed by a transient augmentation of the synaptic potentials after washing of ATP. The actions of ATP on the synaptic potentials were prevented by pretreatment with theophylline, caffeine, quinidine and 8-phenyl theophylline. The ATP analogues, ATP-gamma-s (100 nM-100 microM) and alpha-beta-methylene ATP (100 nM-100 microM) also depressed the synaptic potentials recorded from both types of neurons. The inhibitory effect of adenosine on the synaptic potentials was 10 times weaker than that of ATP. Thus, it seems clear that the presynaptic inhibition is not occurring through adenosine A1 or A2 receptors. Furthermore, ATP at high concentrations ( > or = 1 microM) augmented nicotinic fast depolarizations of S neurons produced by extracellular acetylcholine. However, ATP at the same concentrations inhibited the slow depolarizations of S and AH neurons caused by exogenous acetylcholine (muscarinic) and substance P. It is concluded that ATP regulates synaptic transmission in the myenteric plexus of the guinea-pig ileum and the sites of ATP actions are pre- and postsynaptic.
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PMID:ATP regulates synaptic transmission by pre- and postsynaptic mechanisms in guinea-pig myenteric neurons. 751 68

Male rats were treated i.p. with either 5 mg/kg amphetamine, 3 and 30 mg/kg cocaine or 100 mg/kg caffeine and killed after 30 min. Brains were sectioned and processed for radioactive in situ hybridization histochemistry for the labelling of either c-fos, enkephalin, substance P, neurokinin B, choline acetyltransferase, somatostatin or adenosine A2A receptor messenger RNA. The distribution of c-fos messenger RNA was investigated both at the regional level using film autoradiography, and at the cellular level using emulsion autoradiography. All drug treatments except 3 mg/kg cocaine induced an increased level of c-fos messenger RNA in cells that had a neuron-like morphology. The cells that contained the c-fos messenger RNA were identified by making pairs of 5-microns sections in which one section was processed for c-fos messenger RNA and the other was processed for one of the other messenger RNA species. After amphetamine treatment, only some 10% of the cells in the striatum were labelled, and to a variable extent. Instead there was prominent labelling of a band in the cortex that runs parallel to the cortical surface. There was also a moderate degree of labelling in the nucleus accumbens. c-fos-positive cells were substance P-positive and negative for enkephalin or A2A receptor messenger RNA. Cocaine (30 mg/kg) induced a modest labelling in the caudate-putamen, as well as in the accumbens. With cocaine treatment (30 mg/kg), about 30% of striatal neuron-like cells were c-fos labelled. Most c-fos-positive cells were substance P-positive, but none of the c-fos-positive cells were enkephalin-positive or A2A-receptor-positive. Cocaine (3 mg/kg) had no significant effect on c-fos. Caffeine gave rise to a strong hybridization signal in the caudate-putamen, particularly the dorsolateral part. No other region examined differed significantly from control. With caffeine treatment, about 73% of neuron-like cells were c-fos labelled in the lateral striatum, but labelling was much less pronounced in the medial part or in the accumbens. c-fos-labelled cells were found in enkephalin-positive and enkephalin-negative, substance P-positive and substance P-negative, neurokinin B-positive and neurokinin B-negative groups. No choline acetyltransferase-positive or somatostatin-positive cells were found that were also c-fos-positive with any of the treatments. We conclude that each of the different CNS stimulant drugs induces a highly specific pattern of c-fos messenger RNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differences in the regional and cellular localization of c-fos messenger RNA induced by amphetamine, cocaine and caffeine in the rat. 752 Jan 34


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