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 injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 microgram to 100 micrograms per rat (ED 50: 1.5 microgram/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 microgram to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 micrograms/rat) or i.p. (0.5 mg/kg) injections of naloxone.
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PMID:Intrathecal substance P depresses the tail-flick response - antagonism by naloxone. 617 Aug 95

[D-Pro2, D-Trp7,9]-substance P, an analogue of the putative nociceptive primary afferent neurotransmitter substance P, was administered to rats via chronically implanted intrathecal catheters (0.5-2.5 nmol per rat). Several animals showed large elevations of thermal and mechanical nociceptive thresholds, but these effects were always accompanied by profound, often long-lasting, impairments of motor function and thus cannot be regarded as a specific antinociceptive effect of the drug. These behavioural effects are considered to be probably due to direct spinal actions of the drug rather than antagonism of spinal substance P systems.
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PMID:The behavioural effects of intrathecally administered [D-PRO2, D-TRP7,9]-substance P, an analogue with presumed antagonist actions, in the rat. 618 71

Drug addicts abusing heroin substitutes contaminated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and perhaps those who work with this substance, may develop symptoms similar to those seen in Parkinson's disease [7, 12, 13]. We describe the results of a study in which rats were given daily injections of MPTP for two weeks. A progressive suppression of activity was seen, but the subjects rapidly recovered when treatment ceased. The animals were then injected with D-amphetamine or apomorphine; the former drug enhanced activity, to levels seen in control (non-MPTP treated) subjects. Apomorphine had no effect, either on control or MPTP-treated subjects. The effects of acute (0, 2.5, 5.0 and 10.0 mg per rat) administration of MPTP were also studied. The two lower doses significantly decreased activity, but the highest dose did not. Histological examination showed that 2 weeks' treatment with MPTP did not produce neuronal degeneration in the pars compacta of the substantia nigra (SN). In these animals, there were no changes in levels of dopamine, 5-hydroxytryptamine, or their metabolites in either the SN or the caudate nucleus. MPTP had no effect on the levels of neurotensin, somatostatin and substance P in several brain areas. It is concluded that MPTP has reliable effects on locomotor activity in rats without producing measurable histological or neurochemical changes in the nigrostriatal dopaminergic system.
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PMID:N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigrostriatal lesion in the rat. 633 3

The interrelationship between somatostatin and its synthetic analog, sandostatin, with neuropeptides and inflammatory mediators, as well as their protection of gastric mucosal damage, were tested in rats. Rats were treated intragastrically with 1.0 ml of 96% ethanol with or without intravenous or intraperitoneal coadministration of somatostatin (1.0 microM/kg). Mucosal damage was also induced by the administration of either indomethacin (30 mg/kg subcutaneously) with or without intravenous sandostatin (10 micrograms/rat), given 30 min prior to damage induction. Somatostatin levels in ethanol-damaged gastric mucosa were significantly lower than in control rats. Substance P and vasoactive intestinal peptide (VIP) levels were significantly higher in the damaged mucosa in rats treated with ethanol, as was the mucosal generation of leukotriene B4 (LTB4) and cysteinyl-containing leukotrienes. The coadministration of somatostatin with ethanol significantly reduced gastric mucosal injury induced by ethanol alone. The protection of the mucosa was accompanied by reduction of mucosal substance P and VIP levels, as well as the generation of leukotrienes, an effect that was reversed by intraperitoneal or intravenous coadministration of somatostatin antagonist, cyclo-(7-aminoheptanoyl-PH-E-D-Trp-Lys-THR), 1.0 microM/100 g, with somatostatin (1.0 microM/kg) and ethanol. When given by itself somatostatin significantly reduced mucosal leukotriene generation compared with their generation in saline-treated rats. Sandostatin completely abolished gastric mucosal damage induced by indomethacin administration. In rats treated with somatostatin and indomethacin, this effect was accompanied by reduction of mucosal leukotriene generation. Administration of sandostatin to pylorus-ligated rats significantly reduced gastric acid output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin effectively prevents ethanol- and NSAID-induced gastric mucosal damage in rats. 751 Jun 7

The rat given an intrathecal injection of capsaicin (0.3-10 nmol/rat) through a lumbar puncture showed biting or licking the tail and hind paws. The substance P antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin (10 nmol/rat), caused a significant inhibition of the behavioral responses to capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10 nmol/rat) -induced behavioral responses were significantly inhibited. A co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral responses produced by capsaicin (10 nmol/rat). Administration of the combination of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when either antagonist was co-administered with capsaicin. The results suggest that aversive behaviors induced by intrathecal capsaicin are mediated not only by the activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.
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PMID:Involvement of substance P and excitatory amino acids in aversive behavior elicited by intrathecal capsaicin. 751 12

To determine the role of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examined the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3-3 nmol/rat), the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV, 1-10nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) suppressed RCS-induced hyperalgesia in a dose-dependent manner, without affecting the nociceptive threshold of normal rats. Combinations of any two of CP-96,345 (3 nmol/rat), APV (10 nmol/rat), and CNQX (10 nmol/rat) did not produce a larger inhibition than that produced by their single doses. The present results suggest that the enhancement of the substance P-NK-1 receptor system and glutamate-NMDA and non-NMDA receptor systems in the spinal dorsal horn is at least partly involved in the RCS-induced hyperalgesia.
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PMID:Effects of intrathecally injected glutamate and substance P antagonists on repeated cold stress-induced hyperalgesia in rats. 753 76

1. The topical application of bradykinin (BK) (0.05-5000 pmol/rat) onto the serosal surface of the urinary bladder in urethane-anaesthetized rats, evoked low amplitude tonic contractions (not exceeding 25 mmHg) or high amplitude (about 50 mmHg), phasic reflex contractions (chemoceptive micturition reflex) which were abolished by bilateral ablation of the pelvic ganglia. In ganglionectomized rats, BK induced only a local, tonic-type contraction. 2. Systemic capsaicin pretreatment (164 mumol kg-1, 4 days before) reduced the incidence of chemoceptive reflex induced by BK (500 pmol/rat) but had no effect on the magnitude of the tonic-type contraction elicited by BK in ganglionectomized rats. Indomethacin (11 mumol kg-1, 20 min before) reduced the incidence but not the amplitude of the reflex contractions induced by topical application of BK (500 pmol/rat). In ganglionectomized rats, indomethacin (11 mumol kg-1, 20 min before) decreased the amplitude of the tonic contraction evoked by BK. Indomethacin did not affect the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat) onto the bladder. 3. Intrathecal administration of the tachykinin NK1 receptor antagonists, RP 67,580 (10 nmol/rat) or SR 140,333 (10 nmol/rat), abolished the chemoceptive reflex induced by BK without modifying the magnitude of the tonic contraction. SR 140,333 (10 nmol/rat) also abolished the occurrence of the chemoceptive reflex induced by capsaicin. 4. Intravenous administration of the B2 receptor antagonist, Hoe 140 (35 nmol kg-1, 10 min before) abolished the reflex and local effects induced by BK on bladder motility but failed to modify the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat). 5. Intrathecal administration of Hoe 140 (10 nmol/rat) reduced the incidence of the chemoceptive reflex induced by BK but had no effect on the amplitude of the local motor response. Likewise, Hoe 140(10 nmol/rat, i.t.) reduced the incidence of reflex bladder contractions induced by topical application of capsaicin (15 nmol/rat) without affecting the magnitude of the tonic-type contraction.6. These findings indicate that BK stimulates motility through B2 receptors in the rat urinary bladder.BK activates the reflex response by stimulating capsaicin-sensitive afferent nerves with a contribution from prostanoids. At the spinal cord level, tachykinin NK1 and BK B2 receptors could also be involved in the chemoceptive reflex induced by BK or capsaicin.
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PMID:Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo. 753 95

The selective NK3 tachykinin agonist senktide evokes in rodents 5-HT mediated behaviors, including 5-HT2 receptor-mediated wet dog shakes (WDS) and head shakes (HS). It was observed previously that genetically selected Sardinian alcohol-preferring (sP) rats show a small number of WDS and HS following intracerebroventricular (ICV) injection of senktide. The present study was aimed at confirming these observations and at providing information on the reasons accounting for the anomalous response of sP rats. Senktide (500-2000 ng/rat, ICV) produced a much lower number of WDS and HS in sP rats than in nonselected Wistar (nsW) rats. Both behaviors were suppressed by the 5-HT2 antagonist ritanserin (1 mg/kg, subcutaneously), confirming that 5-HT2 receptors mediate the response. HS induced by the ICV injection of 5-HT agonists endowed with marked activity at 5-HT2 receptors, such as quipazine (1500-6000 ng/rat) or DOI (500-3500 ng/rat), were much less pronounced in sP rats than in nsW rats. Moreover, WDS following peripheral injection of 5-hydroxytryptophan, 25-100 mg/kg, and carbidopa, 12.5 mg/kg, were less intense in sP and in ethanol-naive sP rats than in nsW and in Sardinian alcohol-nonpreferring rats. These findings suggest that sP rats have an inherent different regulation of central 5-HT2 mechanisms.
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PMID:Low responsiveness to agents evoking 5-HT2 receptor-mediated behaviors in Sardinian alcohol-preferring rats. 754 92

Antibody-coated microprobes have provided evidence for the release of neuropeptides in localized regions of the cat spinal cord. We have applied this method to study the release of substance P (SP) from different regions of the rat brain. Anti-SP microprobes were inserted (to a depth of 8 mm) through cortex, striatum, and nucleus accumbens of halothane anaesthetised rats and remained in situ for 10 min. Microprobes (4 control and 10 post-treatment, per rat) were then incubated with 125I-SP and an autoradiographic image produced. In the region of the nucleus accumbens immunoreactive (ir) SP was detected during the first 30 min after intraperitoneal injection of d-amphetamine (4 mg/kg, P < 0.05) but not following saline (P > 0.05). During this time, no release of ir SP was seen over areas of the probes that corresponded to the striatum. At later time intervals (1-4 h) after amphetamine, binding of ir SP was detected along the whole length of the microprobes. Release of SP is thought to be due to the action of dopamine on postsynaptic cells containing this peptide. The later spread of the peptide requires further study.
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PMID:Substance P release from rat nucleus accumbens and striatum: an in vivo study using antibody microprobes. 768 34

The ability of the selective tachykinin NK1 and NK2 receptor agonists, [Sar9] substance P (SP) sulfone and [beta Ala8] neurokinin A (NKA), respectively, and neurokinin B (NKB) to stimulate urinary bladder contractions was determined in urethane-anaesthetized rats with intact bladder innervation and in animals with acute, bilateral ablation of pelvic ganglia. In addition, tachykinin receptors mediating the response to the agonists were characterized by means of the non-peptide NK1 and NK2 receptor selective antagonists, RP 67,580 and SR 48,968 respectively. In both experimental conditions (normal and ganglionectomized), the three tachykinin agonists induced a dose-dependent increase in intravesical pressure, however reflex bladder contractions were produced by the agonists only in animals with intact bladder innervation. RP 67,580 (10 mumol/kg, i.v.) reduced the response to [Sar9]SP sulfone (50 pmol/rat) in both preparations without modifying the effects induced by the NK2 receptor agonist. On the other hand, SR 48,968 (1 mumol/kg, i.v.) antagonized responses induced by [beta Ala8] NKA (50 pmol/rat) but not those evoked by [Sar9] SP sulfone. In animals with intact urinary bladder innervation, the effect of NKB (50 pmol/rat) was inhibited by SR 48,968 (1 mumol/kg, i.v.) but not by RP 67,580; on the contrary, in rats with ablation of pelvic ganglia, the direct bladder contraction induced by NKB was reduced by RP 67,580 (10 mumol/kg, i.v.) but not by SR 48,968. We conclude that NKB induces reflex and direct bladder muscle contractions by stimulating NK2 and NK1 receptors, respectively.
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PMID:In vivo effects of neurokinin B on rat urinary bladder motility: involvement of tachykinin NK1 and NK2 receptors. 796 19


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