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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 181-187 
    ISSN: 1432-1912
    Keywords: Substance P ; Eledoisin ; Substance P antagonists ; Acetylcholine release ; Substance P receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of substance P and eledoisin on spontaneous and electrically-evoked release of [3H]acetylcholine, and on smooth muscle were studied in the guineapig myenteric plexus-longitudinal muscle preparation preloaded with [3H]choline. Substance P and eledoisin caused transient increases in spontaneous release of [3H]acetylcholine and in longitudinal muscle tone. Both tachykinins were equipotent in contracting the muscle, but eledoisin was more potent than substance P in eliciting [3H]acetylcholine release. The release caused by substance P was enhanced in the presence of naloxone and scopolamine which suggests that the release is modulated through opioid and muscarinic receptors. 2. Substance P and eledoisin inhibited the release of [3H]acetylcholine evoked by electrical stimulation at 0.1 Hz. The inhibition was not due to an activation of α-adrenoceptors, histamine or opioid receptors. The substance P antagonists (d-Pro2, d-Trp7,9)SP (10 and 30 μM) and (Arg5, d-Trp7,9, Nle11)SP5–11 (1 and 10 μM) competitively antagonized both the contractile effects of substance P and eledoisin, and the inhibition by the tachykinins of the electrically-evoked release of [3H]acetylcholine. The increase in spontaneous [3H]acetylcholine release elicited by substance P and eledoisin was not prevented by the substance P antagonists. 3. The results suggest that the neuronal receptor whose activation causes inhibition of acetylcholine release and the smooth muscle receptor correspond to the SP-P type, whereas the neuronal receptor mediating an increase in spontaneous acetylcholine release is of the SP-E type. The two antagonists, (d-Pro2, d-Trp7,9)SP and (Arg5, d-Trp7,9, Nle11)SP5–11, selectively block only the SP-P receptor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Substance P ; Kassinin ; Histamine ; Tachykinin agonists ; Tachykinin antagonists ; Tachykinin receptors ; Phosphoinositide metabolism ; Accumulation of inositol phosphates ; Contraction mechanism ; Intestinal smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effect of the tachykinin antagonist, [abetd-Pro4, abetd-Trp7,9,10]substance P-(4–11), on inositol phosphate accumulation produced by tachykinins and by histamine in strips of longitudinal muscle from the guinea-pig small intestine was investigated in the presence of 12 mM Li+. 2. The two tachykinins substance P (SP) and kassinin (20 nM – 20 μM) caused an accumulation of inositol phosphates in a concentration-dependent manner. This was seen with an agonist contact time of only 30 s. SP and kassinin were roughly equipotent in inducing inositol phosphate accumulation, which is consistent with their relative potencies in causing muscle contraction. 3. The tachykinin antagonist (20 μM) produced a shift to the right of the dose-response curves for inositol phosphate accumulation caused by SP and kassinin. However, the effect of kassinin was inhibited much more than that of SP, which is consistent with a similar differential antagonism of the contractions induced by these agonists. 4. The tachykinin antagonist also depressed histamine-induced accumulation of inositol phosphates whereas histamine-induced contractions had previously been found unaffected by the antagonist. 5. These findings show that the tachykinin antagonist is not totally selective with regard to agonist-induced accumulation of inositol phosphates in intestinal smooth muscle. This may suggest that the antagonist not only acts on tachykinin receptors but also has another site of cellular action.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 214-220 
    ISSN: 1432-1912
    Keywords: Intestinal smooth muscle ; Contraction ; Intracellular signalling ; Desensitization ; Substance P ; Histamine ; Phorbol-12,13-dibutyrate ; Polymyxin B
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) This study investigated a possible involvement of protein kinase C (PKC) in the substance P-induced contraction of the longitudinal muscle of the guinea-pig isolated ileum. (2) The predominant effect of the PKC activator, phorbol-12,13-dibutyrate (PDB), was to change the time course of the response to substance P. While the initial peak contraction was hardly influenced by PDB, the fading of the contraction was accelerated to an extent that any tonic contraction which normally followed the initial peak response was prevented. This inhibitory effect of PDB on the tonic contraction was immediate in onset and related to its concentration (20–200 nM); responses to half-maximally (2–7 nM) or maximally effective (0.74 μM) concentrations of substance P were affected in the same manner. Tetrodotoxin (0.6 μM) did not alter the effect of PDB. Phorbol-13-monoacetate (2 μM), a phorbol ester which does not stimulate PKC, failed to change the time course of the substance P-induced contraction. (3) The tonic component of half-maximal contractile responses to histamine (0.20.4 μM) was also depressed by PDB (0.2 μM) whereas the tonic component of maximal responses to histamine (9 μM) was enhanced. (4) PDB (0.2 μM) reduced desensitization to substance P as judged by the reduction of the peak response to substance P (2–7 nM) following a 10-min exposure to a high concentration of the pepide (0.74μM). (5) The PKC inhibitor, polymyxin B (0.1–0.3 mM), reduced the peak contractile response to substance P, slowed the fading of the contraction, and antagonized the inhibitory effect of PDB on the tonic contraction. (6) These findings suggest that, in intestinal smooth muscle, the phasic and tonic components of receptor-mediated contractions involve separate signalling mechanisms. The tonic component of contraction appears to be under the control of protein kinase C which determines whether the contraction fades away or is sustained. Fading of the substance P- induced contraction does not seem to reflect desensitization of the muscle to this agonist.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Peptides 4 (1983), S. 451-455 
    ISSN: 0196-9781
    Keywords: Biliary system ; Cat ; Guinea-pig ; Humans ; Mucosa ; Rabbit ; Radioimmunoassay ; Respiratory system ; Skin ; Substance P ; Sympathetic nervous system ; Urinary system
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 320 (1982), S. 217-220 
    ISSN: 1432-1912
    Keywords: Substance P ; Intestinal muscle ; Mammals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The contractile effect of substance P was examined on the longitudinal muscle of isolated sections of the gut of cat, guinea-pig, pig, rabbit, and rat. Substance P caused contraction of all intestinal regions investigated, but there were marked qualitative and quantitative differences in the contractile responses to substance P. Low concentrations of substance P that did not cause tonic contraction (0.22–2.2 nM), increased the phasic longitudinal contractions observed in the ileum of cat, pig, and rabbit. Higher concentrations induced a tonic longitudinal contraction of the ileum, which in the cat, pig and rat was accompanied by facilitation and in the rabbit by inhibition of the phasic contractions. While in the ileum of guinea-pig and rabbit the maximal longitudinal contraction induced by substance P was equal to the maximal effect of acetylcholine, the maximal response to substance P was only about 50% of that to acetylcholine in the ileum of cat, pig, and rat. The jejunum, ilcum and colon of the rabbit responded to substance P and acetylcholine with similar maximal contractions, but the jejunum appeared to be most and the ileum least sensitive to substance P. The results suggest qualitatively and quantitatively different roles of substance P in the intestinal motility of different mammals.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 305 (1978), S. 9-16 
    ISSN: 1432-1912
    Keywords: Substance P ; Elimination ; Bacitracin ; Salivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Substance P (SP) was infused at different sites of the circulation of the rat. The animal's own salivary response was used as a bioassay to assess the amount of SP not eliminated when SP was infused into different vascular regions. 2. The highest degree of elimination of SP occurred in the liver and in the hind limbs, followed by the kidney. Elimination was low in the lungs and absent in the cerebral vessels. 3. SP was destroyed by rat plasma in vitro. This was a temperature dependent process. 4. Simultaneous infusion of bacitracin potentiated the effect of SP on salivary secretion. The degree of potentiation was dependent on the dose of bacitracin. It acted presumably by inhibiting the enzymatic inactivation of SP in the liver and in peripheral vascular beds. An interaction between bacitracin and SP on the SP receptors of the salivary glands could be excluded. 5. In contrast to the pronounced inhibition of the inactivation of SP by bacitracin in vivo, the in vitro inactivation of SP by rat plasma and in the isolated perfused rat hind quarter was hardly influenced by bacitracin. These results indicate an inactivation of circulating SP both by bacitracin sensitive and bacitracin insensitive enzymes. 6. The high degree at which SP is eliminated in the liver raises the question whether sufficient intestinal SP with be able to reach a distant organ to exert there a hormonal action or whether the SP present in the intestinal tract acts only locally.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 317 (1981), S. 67-70 
    ISSN: 1432-1912
    Keywords: Substance P ; Histamine ; 5-Hydroxytryptamine ; Mast cells ; Rat hindquarter perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The basic peptide substance P causes histamine release from peritoneal mast cells of the rat in vitro whereas the closely related neutral peptides eledoisin and physalaemin do not. 2. Infusion of substance P (7.4 nmol min−1), but not of eledoisin (8.4 nmol min−1) or physalaemin (7.9 nmol min−1), into the rat hindquater preparation caused a more than 4-fold increase of the histamine content in the venous outflow. The outflow of 5-HT remained unchanged under infusion of all three peptides. 3. No histamine depletion in the skin of the rat hind paw was observed following antidromic stimulation of the saphenous nerve or cutaneous application of mustard oil. Infusion of substance P (7.4 nmol min−1) caused a 47% depletion of histamine in the paw skin although only a small proportion of the infused substance P seemed to enter the tissue from the blood vessels. 4. The results further substantiate the view that substance P upon release from peripheral nerve endings induces release of histamine from cutaneous mast cells, a mechanism which contributes to neurogenic vasodilatation and plasma extravasation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1912
    Keywords: Peristaltic reflex ; Atropine-resistant peristalsis ; Guinea-pig ileum ; Substance P ; Cholecystokinin octapeptide ; Bombesin ; Neurotensin ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Slow peristalsis (less than one peristaltic wave/min) was induced by continuous elevation of intraluminal pressure in vascularly perfused segments of the guinea-pig isolated ileum. The intraluminal pressure at the aboral side of the segment and the volume of fluid propelled by each peristaltic wave were recorded. 2. Intraarterial infusion of substance P (11.5–115 pmoles min−1), cholecystokinin octapeptide (CCK-8; 1.5–15 pmoles min−1), bombesin (1–10 pmoles min−1), and neurotensin (3.6–36 pmoles min−1) dose-dependently stimulated peristalsis, the degree of stimulation being largest with CCK-8. Histamine, a drug contracting the smooth muscle directly, did not stimulate peristalsis. 3. Atropine (1 μM in the bath and perfusion solution) caused a transient inhibition or blockade of the peristaltic reflex, followed by a partial recovery of peristalsis (“atropine-resistant peristalsis”). Atropine-resistant peristalsis was greatly stimulated by CCK-8 (6–15 pmoles min−1), only slightly stimulated by bombesin (4 pmoles min−1), and first stimulated and then inhibited by neurotensin (36 pmoles min−1). 4. Substance P (11.5–1,000 pmoles min−1) inhibited or abolished atropine-resistant peristalsis, which was probably due to desensitization of intestinal smooth muscle and/or neurones against the peptide. [d-Pro2, d-Trp7,9] substance P, an analogue of substance P with antagonistic properties (40 nmoles min−1), also inhibited atropine-resistant peristalsis. 5. Naloxone (4.6 nmoles min−1) stimulated peristalsis both in the absence and in the presence of atropine; this indicates that endogenous opioids modulate peristaltic motility. 6. It is concluded that neuropeptides stimulate peristalsis by exciting intramural cholinergic and non-cholinergic neurones. The inhibitory actions of substance P desensitization and of the substance P antagonist in the presence of atropine indicate that substance P neurones play a role in the mechanism af the atropine-resistant peristalsis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 50-55 
    ISSN: 1432-1912
    Keywords: Substance P ; Phosphoinositide metabolism ; Intestinal smooth muscle ; Stimulus-effect coupling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effect of substance P on the metabolism of membrane phosphoinositides and the possible role of this effect in the contractile response to substance P was investigated in longitudinal muscle strips obtained from the guineapig small intestine and prelabelled with [3H] inositol. 2. Substance P (2.2 μM) failed to change significantly the tissue content of phosphoinositides but caused an accumulation of their water-soluble hydrolysis products, inositol bis-phosphate (InsP2) and inositol monophosphate (InsP). These experiments were carried out in the presence of Li+ (12 mM), since only under these conditions could an accumulation of InsP2 be observed. 3. The rate at which InsP2 and InsP accumulated was highest during the first 0.5 min of exposure to substance P (2.2 μM) and then decreased rapidly. Thus, the rate of inositol phosphate accumulation paralleled the time course of the contractile response to substance P. 4. The magnitude of inositol phosphate accumulation was related to the concentration of substance P (22 nM-22 μM). 5. The substance P-induced accumulation of InsP2 and InsP was not reduced when muscle strips had been incubated in Ca2+-free medium, for a time period sufficient to deplete the intracellular Ca2+ store which can be released by substance P, or in Ca2+-free medium containing high [K+]. 6. These findings are compatible with the concept that hydrolysis of membrane phosphoinositides is a mechanism than links substance P receptor activation to contraction but further work is needed to establish a causal relationship.
    Type of Medium: Electronic Resource
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