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)

Substance P (SP), the widely distributed undecapeptide, is synthesized in cell bodies of vagal sensory ganglia and transported bidirectionally toward the CNS and thoracic and abdominal viscera. In explants of the guinea pig inferior (nodose) vagal sensory ganglion and attached 2 cm of distal vagus nerve, SP is synthesized within the ganglion and transported predominantly distally. The quantity of distal transport is similar to that observed in vivo and provides an index of ongoing synthesis within the ganglion. In this report, the model is further characterized. Double ligation of the explant distal to the ganglion demonstrates that all the transported peptide is derived from the ganglion; there is no evidence of intraaxonal processing of peptide precursor. Approximately 50% of the peptide is in a rapid transport vs. an apparent stationary compartment. Not only transport, but also synthesis, of SP was blocked by 20 mM colchicine. Ongoing SP biosynthesis is dependent on a nutrient medium [medium 199 (M-199)] and is partially inhibited with added fetal bovine serum (FBS; 10%): total explant content in M-199/FBS vs. M-199, 1,785 +/- 101 (n = 8) vs. 2,254 +/- 123 pg (n = 9); p less than 0.02. Addition of 2-deoxyglucose (2-DG) decreased both total SP synthesis and transport (total explant content for 2-DG vs. control, 986 +/- 94 vs. 1,391 +/- 111; p less than 0.05). Medium supplemented with glucose to a final concentration of 600 mg/100 ml or with glucose (300 mg/100 ml) with or without insulin (50 ng/ml) did not alter explant SP content or transport. Veratridine (5 X 10(-6) M) inhibited both SP synthesis and transport; ouabain (10(-4) M) also inhibited synthesis, but less so transport. Tetrodotoxin reversed the effects of veratridine. These studies demonstrate the usefulness of this model, which can examine factors regulating both synthesis and transport of sensory neuropeptides in vitro. The results suggest that SP synthesis/transport may be under tonic inhibition, perhaps by both neural and humoral mechanisms.
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PMID:Substance P synthesis and transport in explants of nodose ganglion/vagus nerve: effects of double ligation, 2-deoxyglucose, veratridine, and ouabain. 243 49

The isolated, spontaneously active portal vein of guinea pig was stimulated by the following compounds (the pD2 is given in parentheses): caerulein (CER, 8.02), cholecystokinin octapeptide (CCK-8, 7.59), substance P (SP, 4.68), and carbachol (5.37), whereas neurotensin (NT) was ineffective and angiotensin II (AII) produced inhibition. On the portal vein of the rat, CER and CCK-8 were ineffective, whereas stimulation occurred with SP (5.72), NT (6.79), AII (7.89), and carbachol (5.50). Tetrodotoxin did not modify these effects in both types of preparation. Cyclic dibutyryl guanosine monophosphate reduced the effect of CCK-8 and CER but not that of carbachol. It is concluded that the peptides stimulate the portal vein in a way independent from intramural neurons. It may be speculated that receptors for CCK-8 and CER are absent in the portal vein of rat and those for NT in the guinea pig vein.
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PMID:Cholecystokinin octapeptide, caerulein, substance P, neurotensin, and angiotensin II: species-typical effects on the isolated portal vein of guinea pig and rat. 243 99

We showed previously that electrical transmural stimulation (TS) of guinea pig jejunal mucosa in vitro released neurotransmitters from submucosal plexus neurons which caused alterations in ion transport. The present studies were performed to obtain information regarding the identity of the neurotransmitters. The addition of exogenous substance P (SP) to the serosal side of the tissue caused a transient increase in short-circuit current (Isc) which closely mimicked the response to TS. Both TS and SP caused net secretion of Cl- ions by stimulating movement toward the luminal side. Tetrodotoxin abolished the response to TS, inhibited approximately 70% of the response to SP but did not affect the response to urecholine, a cholinergic muscarinic agonist. In the presence of the muscarinic antagonist, atropine, Isc responses to both TS and SP were reduced suggesting that a portion of both responses was due to action on enteric nerves causing release of acetylcholine. Following desensitization of the tissue with supramaximal doses of SP the response to TS was significantly reduced but the response to urecholine was unchanged. In the presence of atropine, SP desensitization reduced the nerve-stimulated response by approximately 65%; treatment of tissue with SP antibodies reduced the response by approximately 55%. Under the same conditions Isc responses to histamine were unaltered. Our results suggest that both SP (or a structurally analogous neurotransmitter) and acetylcholine as well as additional unidentified neurotransmitter(s) are functionally important in the regulation of intestinal ion transport in guinea pig jejunum.
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PMID:Evidence for substance P as a functional neurotransmitter in guinea pig small intestinal mucosa. 244 2

The effect of bombesin and of substance P was investigated in smooth muscle strips of the chicken crop. Bombesin in picomolar concentration (0.1 x 10(-12) - 5 X 10(-12) mol/l) caused a concentration-related contraction of the muscle strips. Substance P in nanomolar concentration (0.1 x 10(-9) - 10 x 10(-9) mol/l) was effective in the same manner. Tetrodotoxin (2 x 10(-7) mol/l) did not influence the contraction responses to either bombesin or substance P. The excitatory effect of bombesin and of substance P did not follow activation of cholinergic receptors since their effect on the crop smooth muscle was not antagonized by atropine (10(-4) mol/l) or by hexamethonium (10(-4) mol/l). Strips stored for 24 hours in the Tyrode's solution at 4 degrees C without a supply of oxygen maintained their full sensitivity to bombesin and to substance P. These results are consistent with a direct action of bombesin and substance P on the crop smooth muscle.
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PMID:Effect of bombesin and substance P on the smooth muscle of the chicken crop. 246 67

Using an electromyographic technique, an ascending excitatory response was recorded "in vitro" in the presence of atropine in the cat small intestine up to 70 mm orally with respect to the site of repetitive transmural nerve stimulation. This non-cholinergic ascending excitatory response was characterized by an increase in the slow wave amplitude and spiking activity. This response was reversibly abolished by Tetrodotoxin (3,1 X 10(-6) M) but remained unchanged after exposure of the intestine to: Hexamethonium (4,9 X 10(-6) M) plus Tubocurarine (1,4 X 10(-5) M), Guanethidine (5 X 10(-7) to 5 X 10(-5) M), Domperidone (2,3 X 10(-7) to 2,3 X 10(-5) M), Naloxone (3 X 10(-7) to 3 X 10(-5) M), Methysergide (2,8 X 10(-7) to 2,8 X 10(-5) M), Metergoline (2,4 X 10(-5) M), Methiotepin (2,1 X 10(-5) M) and Mepyramine (2,3 X 10(-5) M). This response was unaffected by the substance P analogues, D-Pro2, D-Phe7, D-Trp9-Substance P (10(-5) M) or D-Pro2, D-Trp7-9-Substance P (10(-5) M) but was reversibly abolished after exposure of the intestine to substance P (10(-6) M). Moreover substance P still effectively abolished this response in the presence of any two of the above analogues. The results of the present study show that the non-cholinergic excitatory response elicited in the cat small intestine due to the activity of long ascending pathways probably involved substance P. The functional significance of this response is discussed.
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PMID:Non-cholinergic ascending excitatory response in the cat small intestine: possible involvement of substance P. 246 25

(1) The 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 microM) concentrations of substance P were affected in the same manner. Tetrodotoxin (0.6 microM) did not alter the effect of PDB. Phorbol-13-monoacetate (2 microM), 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 (0.2-0.4 microM) was also depressed by PDB (0.2 microM) whereas the tonic component of maximal responses to histamine (9 microM) was enhanced. (4) PDB (0.2 microM) 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 peptide (0.74 microM). (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.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C may regulate the tonic component of intestinal smooth muscle contraction in response to substance P. 247 Oct 86

Dose-response characteristics of feline corpus circular muscle were studied in vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10(-8) M or 10(-7) M vasoactive intestinal peptide (P less than 0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to greater than or equal to 10(-6) M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P less than 0.001) and reduced responses to substance P (P less than 0.05), but had no effect on responses to cholecystokinin-octapeptide (P greater than 0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.
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PMID:Vasoactive intestinal peptide. An inhibitor of feline gastric smooth muscle in vitro. 247 9

Ruthenium red has recently been found to inhibit the effects of capsaicin on peripheral terminals of sensory neurones. Thus the effects of ruthenium red on the responses of the guinea-pig isolated ileum to capsaicin, acetylcholine (ACh), substance P (SP) and nicotine were investigated. Ruthenium red, 5 mumol/l, abolished responses to capsaicin 1.5 mumol/l and nicotine 2 mumol/l, and shifted the concentration-response lines to ACh and SP to the right. Pretreatment of ileum preparations with ruthenium red, 12.5 mumol/l for 2 min, prevented desensitization of ileum responses to capsaicin tested 30 min later. Tetrodotoxin, 1 mumol/l, abolished the response to capsaicin on control preparations and those pretreated with atropine, 5 mumol/l, ruthenium red, 12.5 mumol/l or spantide, 10 mumol/l. It is proposed that capsaicin acts via a specific receptor coupled to a receptor-operated membrane calcium channel, and that ruthenium red binds irreversibly to the calcium channel part of the complex but reversibly to some other site which prevents the action or binding of capsaicin at its specific receptor.
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PMID:The effects of ruthenium red on the response of guinea-pig ileum to capsaicin. 247 75

The effect and mode of action of substance P was studied in a perfused stomach preparation and on isolated strip preparations of the stomach wall from the rainbow trout, Salmo gairdneri. Substance P was excitatory on the stomach muscle wall in a dose-dependent manner. Two other tachykinins, physalaemin and eledoisin, excited the preparations in a similar manner and in the same dose range. The effect of substance P was not antagonized by the substance P analogues [D-Pro2, D-Phe7, D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P (both 10(-5) M). Tetrodotoxin reduced or abolished the effect of substance P, while no reduction of the response was obtained after atropine, chlorisondamine or phentolamine (all 10(-6) M). 5-Hydroxytryptamine excited the stomach and this effect was not antagonized by tetrodotoxin, suggesting that the action of 5-hydroxytryptamine was direct on the smooth muscle. The 5-hydroxytryptamine antagonist methysergide, in a concentration which selectively blocked the response to 5-hydroxytryptamine, also blocked the response to substance P (10(-9)-10(-8) M). The outflow of 5-[3H]hydroxytryptamine from a preloaded perfused stomach was clearly increased by substance P, and this release was blocked by tetrodotoxin. Immunohistochemistry revealed the presence of nerve fibres and ganglion cells showing 5-hydroxytryptamine-like immunoreactivity in the myenteric plexus and smooth muscle layers of the stomach wall. The immunoreactive cells and nerve fibres were particularly abundant in the pyloric part of the stomach. It is concluded that the main effect of substance P on the stomach wall of the rainbow trout is indirect, via activation of a non-adrenergic, non-cholinergic neuron. The results are compatible with the view that this neuron exerts its action by release of 5-hydroxytryptamine. Supramaximal concentrations (greater than or equal to 10(-7) M) of substance P may in addition have a direct effect on the gastric smooth muscle.
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PMID:Substance P acts by releasing 5-hydroxytryptamine from enteric neurons in the stomach of the rainbow trout, Salmo gairdneri. 258 Nov 71

In vivo and in vitro perfusion techniques have been used to study the release of neurokinin A-like immunoreactivity from the rat substantia nigra. Potassium depolarization and electrical field stimulation evoked calcium-dependent release from nigral slices. Potassium depolarization was also effective in vivo. Tetrodotoxin (1 microM) completely blocked electrically stimulated release but only diminished release in response to depolarizing potassium. Neurokinin A-like immunoreactivity release showed frequency dependence and a clear facilitation phenomenon between 5 and 25 Hz. High-performance liquid chromatography analysis of the immunoreactivity released in vitro revealed the presence of neurokinin A, neuropeptide K and neurokinin B, along with their sulphoxide forms. A marked depletion of neuropeptide K and neurokinin B content was observed when the tachykinin content of the nigral slices was examined before and after stimulation. However, the neurokinin A content of the slices was unchanged or even increased, suggesting an accelerated processing of neurokinin A precursors during the stimulation. The tachykinin peptides were degraded at different rates by substantia nigra homogenates; degradation was fastest for neuropeptide K and slowest for neurokinin A. The addition of a mixture of peptidases inhibitors (thiorphan, phosphoramidon, bestatin and captopril) substantially reduced the degradation of all three tachykinins, but did not completely block degradation. GABA-A receptor antagonists such as bicuculline and, particularly, picrotoxin potentiated the stimulated neurokinin A-like immunoreactivity release in vitro, but the GABA-agonist muscimol had no effect. Picrotoxin was even more potent in vivo. The results presented in this study demonstrate that neurokinin A, neuropeptide K and neurokinin B can be released by depolarizing stimuli from rat substantia nigra. Furthermore, the features exhibited by this release suggest that these peptides may have a neurotransmitter/neuromodulator role in the rat substantia nigra.
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PMID:In vitro and in vivo release of neurokinin A-like immunoreactivity from rat substantia nigra. 290 88


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