Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

The cholinergic and noncholinergic-nonadrenergic (NCNA) excitatory and inhibitory responses of the guinea-pig ileum to transmural nerve stimulation (TNS) were studied. Unlike the contraction induced by histamine and acetylcholine the responses to TNS, ATP, substance P, bradykinin, 5-HT and GABA were not sustained. The contraction and its fading during TNS involved the activation of cholinergic, adrenergic and NCNA neurons. Substance P, 5-HT and ATP desensitization resulted in reduction of the excitatory NCNA response whereas that due to bradykinin attenuated both the excitatory and inhibitory NCNA responses. The desensitization against TNS and the potential transmitters studies was selective except in the case of ATP. The present results suggest that it is unlikely that ATP, bradykinin or GABA would be the NCNA transmitters in the guinea-pig ileum. The cross-desensitization between the excitatory NCNA transmitter on the one hand, and substance P (markedly expressed) and 5-HT (slightly expressed) on the other hand, give further evidence in favor of the possible transmitter role of substance P-like peptide in excitatory NCNA transmission and of the role of 5-HT in the activation of NCNA neurons.
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PMID:Effect of desensitization induced by adenosine 5'-triphosphate, substance P, bradykinin, serotonin, gamma-aminobutyric acid and endogenous noncholinergic-nonadrenergic transmitter in the guinea-pig ileum. 242 32

The contribution of the myenteric plexus in the mechanical responses of rat jejunal longitudinal muscle produced by several enteric nerve substances was evaluated. The myenteric plexus of a segment of rat jejunum was destroyed by serosal application of benzalkonium chloride (BAC). Fifteen days after BAC treatment, both the BAC-treated and an orad control jejunal segment were removed and the mechanical responses of the longitudinal muscle produced by the following substances were examined: substance P, acetylcholine (ACh), 5-hydroxytryptamine (5-HT), cholecystokinin octapeptide (CCK-8), norepinephrine, vasoactive intestinal peptide (VIP), bombesin, [Leu5]enkephalin and somatostatin. Our results indicate that: substance P and norepinephrine produce their mechanical responses by acting predominantly on the longitudinal smooth muscle; 5-HT, CCK-8, ATP, VIP and neurotensin act predominantly through the myenteric plexus; ACh possesses both direct and indirect actions; and because the responses to [Leu5]enkephalin, bombesin and somatostatin were equivocal, a conclusion as to their site of action could not be made with this preparation.
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PMID:Differentiation between myenteric plexus and longitudinal muscle of the rat jejunum as the site of action of putative enteric neurotransmitters. 243 41

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.
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PMID:Spinal antinociceptive effects of adenosine compounds in mice. 244 Jul 5

The cross influence of polypeptides (substance P, eledoisin) and neurotransmitters (acetylcholine, histamine, 5-hydroxytryptamine, ATP) on isolated guinea pig ileum involved a reduction or loss of muscle sensitivity. After the desensitization induced by one of the neurotransmitters the sensitivity of the ileum longitudinal muscle to polypeptides as estimated by the dissociation constant of the drug-receptor complex, decreased, i.e. a non-specific cross desensitization occurred. 5-hydroxytrpyptamine, however, increased the sensitivity to the polypeptides. A similar sensibilizing effect is characteristic of the polypeptides which, after application, increased 1.5-2.0-fold the height of the maximum muscle contraction and decreased 2-4-fold the dissociation constant. A possible involvement of polypeptides not only in their interaction with the target cells but also in the modulation of neurotransmitters, is discussed.
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PMID:[Reciprocal effect of polypeptides and mediators on the ileum of the guinea pig]. 244 Jul 34

Plasma protein extravasation was studied in the rat abdominal skin. Substance P (SP), neurokinin A (NKA) and B (NKB) were found to induce extravasation with a threshold dose of about 1 pmol. Calcitonin gene-related peptide (CGRP) caused no or little extravasation alone but it potentiated the action of SP, NKA, NKB, and physalaemin. The potentiation of the SP-induced extravasation was unaffected by pretreatment with capsaicin, indomethacin or compound 48/80, it was reduced by neuropeptide Y or pretreatment with mepyramine plus cimetidine, and was abolished in streptozotocin diabetic rats. CGRP augmented extravasation induced by histamine, reduced the effect of ATP or adenosine and did not alter extravasation by serotonin, bradykinin or neurotensin. These results indicate that in addition to SP the novel mammalian tachykinins NKA and NKB may be considered as mediator candidates for neurogenic plasma extravasation. CGRP is a possible mediator of antidromic vasodilation. Furthermore, CGRP potentiates the extravasation caused by coexisting tachykinins and could thereby augment neurogenic inflammation. The diverse interactions of CGRP with other inflammatory mediators suggest multiple sites of action.
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PMID:Several mediators appear to interact in neurogenic inflammation. 244 66

1 Capsaicin (Cap) enhanced the twitch response of the epididymal and prostatic portions of rat vas deferens induced by field stimulation at 0.1 Hz. The effect of Cap was reproducible and showed no desensitization. 2 Prazosin, and pretreatment with reserpine or Cap did not affect the potentiating effect of Cap, whereas pretreatment with 6-hydroxydopamine abolished the action of Cap. 3 Cap tended to attenuate the contractions induced by noradrenaline, tyramine and ATP. 4 Like Cap, substance K and substance P augmented the twitch response without causing desensitization, but their effects differed somewhat from that of Cap. Calcitonin gene-related peptide inhibited the twitch response. 5 These results suggest that Cap enhances a stimulation-induced, prazosin-resistant non-adrenergic twitch response of rat vas deferens through an as yet undefined prejunctional mechanism. This mechanism is possibly mediated by some peptide released in response to Cap from sensory neurones, which in turn acts on sympathetic nerves and increases stimulation-induced release of a mediator or cotransmitter responsible for the non-adrenergic twitch response. However, the possibility that Cap has a direct action on sympathetic nerves cannot be ruled out.
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PMID:Capsaicin enhances the non-adrenergic twitch response of rat vas deferens. 244 7

Previous studies have shown that exposure of parotid acinar cells to substance P at 37 degrees C results in activation of phospholipase C, formation of [3H]inositol 1,4,5-trisphosphate (IP3), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to approximately 20% of control values, IP3 formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to approximately 5% of control values, and both IP3 formation and desensitization were blocked. A series of substance P-related peptides increased the formation of [3H]IP3 and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, [D-Pro, D-Trp]-substance P, inhibited substance P-induced IP3 formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP3 formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.
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PMID:Substance P receptor desensitization requires receptor activation but not phospholipase C. 245 23

1. We examined the possibility that the neuropeptide, galanin, may act as a transmitter in longitudinal muscle isolated from the rat ileum. 2. Galanin at nanomolar concentrations produced a phasic contraction with a concomitant increase in rhythmic activity. At concentrations in excess of 3 x 10(-8) M, the contraction was followed by a rapid desensitization; hence, with the cumulative re-addition of galanin, there was no response. This desensitization was probably selective for galanin because there was no attenuation of the contractile responses to substance P, neurokinin A and B, bradykinin or carbachol. 3. The phasic contraction induced by galanin was not inhibited by atropine, guanethidine, hexamethonium, naloxone, tetrodotoxin or [D-Pro2, D-Trp7,9]-substance P. 4. Electrical stimulation of intramural nerves at low frequencies (1-5 Hz) led to an augmentation of spontaneous rhythmic contractions, which were completely or partially inhibited by atropine. However, guanethidine, hexamethonium, naloxone, [D-Pro2, D-Trp7,9]-substance P and desensitization to galanin were without effect on the response to such electrical stimulation. 5. In contrast, transmural electrical stimulation at higher frequencies in the presence of atropine and guanethidine produced biphasic contractile responses with transient and slow components. The slow component was selectively attenuated by galanin desensitization. 6. The slow component induced by high frequency stimulation was markedly attenuated by repeated electrical stimulation at short intervals (2.5 min between 30 s trains). Following repeated stimulation, the contractile response to galanin was also attenuated. Thus, a cross-desensitization between the mediator of the slow component and galanin had to be considered. In contrast, responses to tachykinins and the transient component induced by electrical stimulation were without effect. 7. Somatostatin, vasoactive intestinal polypeptide and alpha,beta-methylene ATP were without effect on the tone of the muscle. Calcitonin gene-related peptide, neurotensin, gastrin-releasing peptide, neuropeptide Y and capsaicin produced either a transient arrest of the spontaneous rhythmic activity or a transient relaxation. 8. These results suggest that the slow component of the non-cholinergic non-adrenergic contraction, as induced by intramural nerve stimulation is apparently due to the endogenous release of galanin, presumably released from galanin-containing nerves in the rat ileum.
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PMID:Contribution of galanin to non-cholinergic, non-adrenergic transmission in rat ileum. 246 26

1. The effect of an acid extract of the carp intestinal bulb (ECI) on guinea-pig ileum longitudinal smooth muscle (GPLM) and carp intestinal bulb longitudinal smooth muscle (CIBLM) was examined. 2. ECI caused a concentration-dependent contraction of GPLM and CIBLM. This ECI-induced response was reduced by atropine to 30-40% of the control, indicating that part of the contracting activity of ECI is attributable to acetylcholine. The atropine-resistant contracting activity of ECI was not mediated by histamine, 5-hydroxytryptamine, ATP, ADP, angiotensin II, neurotensin, vasoactive intestinal peptide or an opioid peptide. 3. The active material mediating the atropine-resistant contracting activity is probably a peptide, because the contraction in response to ECI was abolished on incubation with pepsin or alpha-chymotrypsin. 4. [D-Pro2, D-Trp7,9]-substance P, [D-Pro4, D-Trp7,9]-substance P (4-11) decreased the atropine-resistant contracting activity of ECI as did desensitization induced by substance P. 5. On a Sephadex G 25 column, the active material was eluted as one peak. The active fractions were pooled and then applied to another Sephadex G25 column to compare the Ve/Vo value for the active material with those for peptides of known molecular weights. The molecular weight of the active material was estimated to be 1200-1700 (1410 +/- 70, n = 6). 6. The results indicate the presence of a substance P-like peptide in the carp intestinal bulb.
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PMID:Presence of a substance P-like peptide in an acid extract of the intestinal bulb of the carp (Cyprinus carpio). 246 88


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