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 responsiveness of functionally identified cat spinal dorsal horn neurons to iontophoretically applied substance P (SP) and 5-hydroxytryptamine (5-HT) has been investigated by means of extracellular recording after 5-HT depletion with p-chlorophenylalanine (p-CPA). In addition, the spinal levels of 5-HT, SP, cholecystokinin octapeptide, neurotensin, and vasoactive intestinal polypeptide have been measured in intact and p-CPA-pretreated cats. In the present study we have demonstrated an altered responsiveness of dorsal horn neurons to locally applied SP and 5-HT. We found in p-CPA-pretreated cats that the proportion of neurons responding with excitation to SP and 5-HT was significantly increased. At the same time, depression induced by 5-HT in the dorsal horn cells was virtually absent in p-CPA-pretreated animals. Our finding that spinal level of 5-HT was significantly decreased in p-CPA-treated animals is consistent with previous studies. No convincing alteration in the spinal levels of 4 analyzed peptides was found in p-CPA-treated animals. The present study has shown that pharmacological depletion of 5-HT has two major effects: (1) it increases significantly the proportion of dorsal horn neurons excited by SP and 5-HT; and (2) it is ineffective in inducing 5-HT supersensitivity. Further work is needed to explain mechanisms involved in these effects.
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PMID:Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine. 242 Apr 13

The behavioural response to intrathecally injected substance P (SP, 1.25 ng) was investigated in mice after lesioning of serotonergic (5-HT) pathways by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms base/mouse) and after 5-HT synthesis inhibition by p-chlorophenylalanine (PCPA, 400 mg kg-1 for 6 consecutive days). Pretreatment with 5,7-DHT and PCPA reduced the 5-HT level in the spinal cord to 6 and 7% of controls and the noradenaline (NA) level to 69 and 84% of controls, respectively. Intrathecally injected SP produced a response consisting of vigorous biting, licking and scratching of the caudal part of the body. The response to SP was significantly increased 5 days after injection of 5,7-DHT, but only a non-significant tendency towards enhancement of the response was found after 24 h. There was no change in the response to SP 24 h after the last injection of PCPA. It is suggested that 5,7-DHT but not PCPA induces receptor supersensitivity to SP, and that reduction in spinal SP by 5,7-DHT may be a factor in this change in receptor sensitivity.
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PMID:Increased behavioural response to intrathecal substance P after intracerebroventricular 5,7-dihydroxytryptamine but not after p-chlorophenylalanine administration. 246 67

In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.
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PMID:Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol. 294 27

Since substance P (SP) has been demonstrated to coexist with serotonin (5-HT) in the same population of neurons in the descending raphe system, we have studied the possibility of interactions between these neurotransmitters in other brain areas. Brain nuclei were punched from frozen 300-micron slices of rat brain and extracted with 0.1 M HCIO4 or 2 M acetic acid prior to assay, respectively, of 5-HT content by HPLC with electrochemical detection or SP content by specific radioimmunoassay. Ten days after injection of rats with the 5-HT neurotoxin P-chloroamphetamine (PCA, 10 mg/kg, B.W., i.p.) or 3 days after 5-HT synthesis blockade with p-chlorophenylalanine (PCPA, 300 mg/kg, B.W., i.p.), the 5-HT content of all brain nuclei studied was reduced by means of, respectively, 50% and 81%. In PCA-treated animals, the SP content of the periaqueductal grey matter was significantly increased; PCPA treatment caused, in addition, large increases in the SP content of five other brain nuclei. Blockade of 5-HT receptors by methysergide (15 mg/kg for 5 days) did not significantly change 5-HT levels or turnover, but resulted in 50-200% increases in the SP content of 10 of the 28 brain nuclei studied. Significant decreases in the SP content of numerous areas were seen following treatments (pargyline 30 mg/kg, alone or in combination with 5-hydroxytryptophan, 60 mg/kg) that simultaneously increased 5-HT levels. These results illustrate the modulation of distinct SP-containing systems of the rat brain by perturbation of central serotoninergic pathways and indicate a reciprocal relationship between the SP and 5-HT concentrations of numerous brain nuclei, in particular n. striae terminalis, n. raphe dorsalis, n. accumbens, n. septi, substantia grisea centralis, and n. raphes medianus.
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PMID:Perturbation of rat brain serotonergic systems results in an inverse relation between substance P and serotonin concentrations measured in discrete nuclei. 619 16

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the content of substance P and TRH in the lumbar segment of the rat spinal cord were studied. The peptide content of discrete spinal cord regions removed by punches of frozen serial slices was measured by RIA. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. In hypothyroid animals without PCPA-treatment, levels of TRH and substance P were significantly increased by 100% in the ventral and the dorsal lumbar spinal cord, respectively. Inhibition of serotonin biosynthesis by PCPA increased by 90% the substance P content in the dorsal horn of euthyroid rats and abolished completely the stimulatory effect of hypothyroidism on the TRH content of the ventral horn. These findings suggest the existence of a physiological relationship between substance P and TRH with the serotoninergic system in the rat spinal cord and that thyroid hormone is implicated in the normal development of the peptide-containing neurons in the rat spinal cord.
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PMID:Comparative effects of neonatal hypothyroidism and euthyroidism on TRH and substance P content of lumbar spinal cord in saline and PCPA-treated rats. 619 82

Neurotransmitters such as serotonin (5HT) may have nontransmitter, trophic-like functions in the developing and adult nervous system. In order to examine this possibility in the avian spinal cord, we have quantified synapse numbers on spinal neurons following treatment with drugs that result in the destruction of 5HT positive axons. Either p-chlorophenylalanine or reserpine was injected into newly hatched or adult chickens. Following treatment for 7 days the density of nonserotoninergic synapses was considerably decreased in the targets of 5HT fibers. By contrast, neither change was observed in the dendritic structures of spinal motoneurons or in the distribution of substance P and enkephalin positive fibers. These data suggest that 5HT may play an important role in the normal increase and maintenance of synapses in developing and adult animals. A lesion of 5HT neurons may not only alter neurochemistry but also alter the general synaptic structures of the brain. While 5HT containing fibers were depleted in a dose-dependent fashion we cannot rule out the possibility that other neurotransmitter systems were depleted at higher dose of PCPA and reserpine.
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PMID:Synaptic loss following removal of serotoninergic fibers in newly hatched and adult chickens. 768 66

1. The aim of this study was a pharmacological characterization of the multiple NANC inhibitory transmission systems producing relaxation of the circular muscle of guinea-pig proximal colon. In the presence of atropine (1 microM), guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a cumulative frequency-response curve, the maximal relaxant effect was produced at 3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS-evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG, was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2. Three protocols of EFS were developed for further pharmacological analysis: (a) EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin-sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin, producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for 5 s in the presence of both apamin and L-NOARG, producing a transient but slowly developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor, thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz in the presence of apamin or L-NOARG. The angiotensin converting enzyme inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L-NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L-NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1 microM) did not affect the EFS-induced NANC relaxations. In the presence of nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced relaxation in the presence of L-NOARG (158% of control) and that produced by 10 Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7. In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM) produced a concentration-dependent, slowly developing relaxation of colonic strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100 microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10 microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the presence of apamin and L-NOARG. 9. The present findings provide evidence that three distinct NANC inhibitory mechanisms mediate relaxation of the circular muscle of the guinea-pig proximal colon. The first system provides a fast relaxation in response to low frequency of stimulation and may involve the action of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels. The second system likewise provides a fast relaxation of the colon in
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PMID:Characterization of the apamin- and L-nitroarginine-resistant NANC inhibitory transmission to the circular muscle of guinea-pig colon. 888 60

1. The contribution of sensory neurons and mast cells to the oedema evoked by adenosine A1 (N(6)-cyclopentyladenosine, CPA, 3 - 30 nmol site(-1)), A2 (5'N-ethylcarboxamidoadenosine, NECA, 1 - 10 nmol site(-1)) and A3 receptor agonists (N6-[3-iodobenzyl]-N-methyl-5'-carboxiamidoadenosine, IB-MECA, 0.01 - 3 nmol site(-1)) was investigated in the rat skin microvasculature, by the extravascular accumulation of intravenously-injected (i.v.) 125I-albumin. 2. Intradermal (i.d.) injection of adenosine and analogues induced increased microvascular permeability in a dose-dependent manner (IB-MECA > NECA > CPA > adenosine). The non-selective adenosine receptor antagonist theophylline (5 - 50 nmol site(-1)) markedly inhibited adenosine, CPA or NECA but not IB-MECA-induced plasma extravasation. The A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 - 3 micromol kg(-1), i.v.) significantly reduced CPA-induced plasma extravasation whereas responses to adenosine, NECA or IB-MECA were unchanged. The A2 receptor antagonist 3,7-dymethyl-1-proprargylxanthine (DMPX, 0.5 - 50 nmol site(-1)) significantly reduced NECA-induced plasma extravasation without affecting responses to adenosine, CPA and IB-MECA. 3. The tachykinin NK1 receptor antagonist (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2]octane chloride (SR140333), but not the NK2 receptor antagonist (S)-N-methyl-N[4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]-benzamide (SR48968), significantly inhibited the plasma extravasation evoked by higher doses of adenosine (100 nmol site(-1)), CPA (100 nmol site(-1)), NECA (1 nmol site(-1)) and IB-MECA (0.1 - 1 nmol site(-1)). In rats treated with capsaicin to destroy sensory neurons, the response to higher doses of adenosine, CPA and NECA, but not IB-MECA, was significantly inhibited. 4. The effects of adenosine and analogues were largely inhibited by histamine and 5-hydroxytryptamine (5-HT) antagonists and by compound 48/80 pretreatment. 5. In conclusion, our results provide evidence that adenosine A1 and A2, but not A3, receptor agonists may function as cutaneous neurogenic pro-inflammatory mediators; acting via microvascular permeability-increasing mechanisms that can, depending on dose of agonist and purine receptor under study, involve the tachykinin NK1 receptor and mast cell amines.
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PMID:The plasma protein extravasation induced by adenosine and its analogues in the rat dorsal skin: evidence for the involvement of capsaicin sensitive primary afferent neurones and mast cells. 1152 2