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)

The characteristics of substance P release have been investigated in the rat substantia nigra, in vitro, using a sensitive radioimmunoassay method. The spontaneous efflux of substance P represented approximately 0.5% of tissue stores released per minute. Addition of potassium to the superfusion medium produced a concentration-dependent increase in substance P release which was linear over the range 15--60 mM potassium. The potassium-evoked release of substance P was almost totally abolished by removal of calcium from the superfusion medium, and was linearly related to an increase in calcium concentration with a corresponding decrease in the magnesium concentrations over the range 0.1--3.0 mM calcium. Veratridine (50 micrometer) also evoked the release of substance P in a calcium- and tetrodotoxin-sensitive manner. Superfusion of substantia nigra slices with GABA produced a concentration-dependent inhibition in the K+-evoked release of substance P which could be abolished by continuous superfusion with picrotoxin. Bicuculline was less effective than picrotoxin in blocking the effects of GABA. The GABA agonist muscimol also produced an inhibition of substance P release, whereas baclofen was without effect. These results support the concept that substance P may function as a neurotransmitter within the substantia nigra, and suggest that GABA may have a role in the regulation of substance P release.
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PMID:Substance P release from the rat substantia nigra. 66 25

Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the cord tissue to 10 microM clonidine and tizanidine significantly reduced the release of substance P. The inhibitory effects of clonidine and tizanidine were attenuated by pre-exposure of the tissue to 10 microM piperoxane, which has alpha 2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10 microM yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for alpha 1- and alpha 2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that alpha 2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.
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PMID:Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists. 171 70

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the release of endogenous acetylcholine was measured using high-performance liquid chromatography with an electrochemical detection system. Application of high-K+ (90 mM) medium evoked about an eight-fold increase in the acetylcholine release, and the K(+)-evoked release was Ca2+ dependent. Veratridine (20 microM) also evoked about a four-fold increase in the acetylcholine release, and this increase was suppressed by 0.2 microM tetrodotoxin. Application of substance P at 0.3-3 microM evoked a concentration-dependent release of acetylcholine. The substance P-evoked acetylcholine release was Ca2+ dependent and abolished by tetrodotoxin. Neurokinin A, neurokinin B, acetyl-Arg6-septide and senktide (3 microM each) also evoked a release of acetylcholine. Electrophysiological experiments using isolated spinal cords of newborn rats showed that bath application of substance P induced a depolarization of motoneurons, which was enhanced by edrophonium. This enhancement of substance P-induced depolarization by edrophonium disappeared in a low-Ca2+ medium or in the presence of atropine and dihydro-beta-erythroidine. In the presence of edrophonium and dihydro-beta-erythroidine, substance P induced an inhibition of monosynaptic reflex, and this inhibition was abolished by atropine. These results suggest that substance P and other tachykinins induce a release of acetylcholine from the newborn rat spinal cord by exciting cholinergic neurons.
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PMID:Substance P-evoked release of acetylcholine from isolated spinal cord of the newborn rat. 172 89

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 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

In order to examine the sensitivity of the nociceptive system of birds to capsaicin, the algesic potency of the drug was compared with that of veratridine and mustard oil by instillation into the eye of conscious pigeons and guinea-pigs. In guinea-pigs, 10(-6) g/ml capsaicin provoked severe protective reactions, but even high concentrations of 10(-2) g/ml were insufficient in pigeons. Veratridine and mustard oil induced similar reactions in both species. Close arterial injections of algesic substances revealed that the threshold dose of capsaicin for cardiovascular and nocifensive reactions was 10,000-fold higher in pigeons (200 micrograms) than in guinea-pigs (0.02 micrograms). All other algesic substances tested (bradykinin, 5-HT, veratridine and KCl) had similar thresholds in both species. Slow infusion of a total dose of 600 mg/kg capsaicin into the radial artery of pigeons did not alter the sensitivity to any of the algesic substances tested, which demonstrates that even high concentrations of capsaicin have no desensitizing effect. The demonstrated insensitivity of pigeons to the algesic effect of capsaicin is discussed in the context of the inability of the drug to deplete substance P (SP) from afferent terminals in the spinal cord of the pigeon.
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PMID:Nociception in pigeons is not impaired by capsaicin. 379 18

Regulation of the putative peptide neurotransmitter substance P was examined in the superior cervical sympathetic ganglion of the neonatal rat. Surgical decentralization (denervation) of the superior cervical ganglion increased ganglion substance P content. In cultured ganglia, the amount of substance P increased more than 50-fold after 48 hours, and this rise was dependent on protein and RNA synthesis. Veratridine prevented the increase in substance P in vitro, and tetrodotoxin blocked the veratridine effect; this suggests that sodium influx and membrane depolarization prevent substance P elevation. Immunohistochemical analysis of cultured ganglia indicated that substance P was present in the perikarya of principal sympathetic neurons and in ganglionic nerve processes. Transsynaptic impulses, through the mediation of postsynaptic sodium influx, may decrease substance P in sympathetic neurons.
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PMID:Substance P in principal sympathetic neurons: regulation by impulse activity. 616 53

Mechanisms regulating the content of the putative peptide transmitters, substance P and somatostatin, were examined in several neuronal populations in culture. Substance P levels increased more than 25-fold within 48 h in sympathetic neurons in the explanted rat superior cervical ganglion, and remained elevated for 4 weeks. Identity of the peptide was authenticated by combined high pressure liquid chromatography-radioimmunoassay. Veratridine prevented the increase of substance P in vitro, and tetrodotoxin blocked the veratridine effect, suggesting that sodium ion influx and membrane depolarization prevent peptide elevation. Veratridine (or potassium)-induced membrane depolarization released substance P into the culture medium through a calcium-dependent process. Consequently, at least some veratridine effects are attributable to release and subsequent depletion of ganglion peptide. However, the inhibitory effects of veratridine were far greater than could be accounted for by the quantity of peptide released, suggesting a separate influence on net synthesis (synthesis less catabolism) of substance P. Viewed in conjunction with previous in vivo studies, our observations suggest that trans-synaptic impulses, through the mediation of postsynaptic sodium flux, release substance P from sympathetic neurons and also regulate intracellular peptide metabolism. To determine whether the processes regulating substance P in sympathetic neurons reflect generalized mechanisms, a different peptide, somatostatin, was examined in sympathetic neurons; moreover, substance P was examined in a different neuronal population, special sensory neurons in the nodose ganglion. Substance P levels increased significantly in both sympathetic and sensory neurons after explantation, and somatostatin levels increased in sympathetic neurons. In each instance, the increase was dependent upon the presence of the calcium ions. Moreover, these increases were all prevented by veratridine, in a tetrodotoxin-sensitive manner. Our observations suggest that common regulatory mechanisms govern peptide transmitter metabolism in diverse neuronal populations.
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PMID:Substance P and somatostatin metabolism in sympathetic and special sensory ganglia in vitro. 619 61

Substance P (SP), the putative neuropeptide mediator of pain sensation, is contained in small dorsomedial sensory neurons of the dorsal root ganglion. Using different culture techniques and a sensitive radioimmunoassay for SP, we studied the ontogeny and regulation of this functionally important neurotransmitter in these neurons, obtained from neonatal rats. In ganglion explants grown by two different techniques, SP increased two- to threefold during the first week in culture. This rise was predominantly due to mechanisms intrinsic to the ganglion since it occurred in a fully defined medium, in the absence of added nerve growth factor (NGF). Blockade of protein synthesis with cycloheximide prevented the increase in SP suggesting that ongoing protein synthesis was necessary. Furthermore, depolarization with veratridine blocked the increase in SP, an effect which was reversed by tetrodotoxin, suggesting that transmitter characteristics in sensory neurons may be regulated by depolarization and/or transmembrane sodium flux. After a week in culture on a collagen substratum, supplementary NGF was necessary for the continued rise in SP. However, raising the dose of the trophic factor had no incremental effect on SP content, suggesting that NGF was acting primarily on neuronal survival. To approach such questions at the cellular level, ganglia were dissociated and grown in cell culture. In all cultures, SP increased 1.5-fold during the first day. In the absence of NGF, however, SP and cell numbers fell progressively after the second day. NGF elicited parallel increases in cell survival and SP content, supporting the suggestion that NGF acts primarily through neuronal survival to increase SP. Veratridine blocked the increase in SP in a tetrodotoxin-reversible manner, without affecting neuronal survival, indicating that the effects of these agents do not depend on normal ganglionic cellular architecture. Consequently, depolarization probably affects ganglionic sensory neurons directly. Our studies suggest that the development of transmitter characteristics in primary sensory neurons may be regulated by multiple factors, including neuronal activity as well as trophic agents such as NGF.
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PMID:Development and regulation of substance P in sensory neurons in vitro. 620 Mar 74

Target organ regulation of the putative, peptide neurotransmitter, substance P (SP) was examined in explants and dissociated cell cultures of the neonatal rat sympathetic superior cervical ganglion (SCG). SP levels increased dramatically in explants, rising more than 30-fold after 72 hr in culture. By contrast, peptide levels did not increase in dissociated ganglion cultures. However, SP increased almost 10-fold in cell cultures grown on a monolayer of cells derived from the pineal or salivary gland, targets of the SCG. By contrast, SP content did not increase in cultures grown on a substrate of cells derived from heart or intestine. Peptide identity in the SCG-target cocultures was authenticated by means of combined high-pressure liquid chromatography (HPLC)-radioimmunoassay. Moreover, immunohistochemical examination localized the peptide virtually exclusively to sympathetic neurons and nerve processes. Mechanisms mediating the sympathetic-target interaction were examined in SCG-pineal cocultures. The increase in peptide required interactions with living tissue, since substrates of killed target cells did not elevate SP levels. The target influences were not mediated by nerve growth factor or indoleamines, potential secretory products of pineal in culture. Veratridine treatment prevented the increase in SP in the cocultures, and tetrodotoxin blocked the veratridine effect, suggesting that sodium influx and membrane depolarization prevent SP elevation. Our observations suggest that sympathetic neuron interactions with target organs influence peptidergic expression, and that this interaction may be restricted to certain appropriate target structures.
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PMID:Target organ regulation of substance P in sympathetic neurons in culture. 620 8


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