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 effects of post-trial injection of substance P (SP) into the lateral hypothalamus (LH) and the ventromedial hypothalamus (VMH) on passive avoidance learning was studied in rats. In the VMH, 50 ng and 500 ng SP influenced neither learning of a step-down avoidance nor of an alcove avoidance response. In contrast to these findings, 500 ng SP injected into the LH significantly enhanced retention of the alcove avoidance task. Similarly, in the step-down avoidance experiment, learning was strongly facilitated by posttrial injection of 50 ng as well as 500 ng SP into the LH. These results, together with our previous data showing amnesia with posttrial injection of SP into amygdala and substantia nigra, suggest that exogenously applied SP influences the activity of those brain regions shown to contain high densities of SP-positive nerve terminals. Interestingly, the effects of posttrial SP injection parallel the effects of post-trial electrical brain stimulation on passive avoidance learning. Hence, posttrial SP retroactively facilitates or impairs learning depending on where in the brain it is injected.
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PMID:Differential effects on learning by ventromedial vs lateral hypothalamic posttrial injection of substance P. 49 93

Formation of experimental neurosis in rats was accompanied in 64% of animals by development of amnesia of conditioned reaction of passive avoidance. Disturbance of mnestic processes was manifested by a change in free amino acids pool including the acids with neurotransmitter properties (GABA, glutamate, glycine). An increase of GABA and glycine content was found in the frontal cortex and an increase of glutamate and GABA--in the hippocampus and striate body. Substance P (125 mkg/kg) administered intraperitoneally against the background of a developed neurosis, produced in 80% of cases an antiamnestic action, accompanied by a statistically significant decrease of GABA content in the frontal cortex, hippocampus and midbrain, and an increase of glutamate in the midbrain. The level of taurine decreased in the frontal cortex, hippocampus and striate body, and increased in the midbrain. Threonine content increased in the striate body and midbrain; there was an increase of taurine, serine and glycine in the midbrain and of glycine in the striate body.
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PMID:[Effect of substance P on the reproduction of memory engrams and on the amino acid composition of brain structures in rats with experimental neurosis]. 246 61

JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
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PMID:JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. 756 10

The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice. Spontaneous alternation performance is based on spatial working memory which produces a natural tendency to explore a less recently visited arm in a Y-maze. Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries. However, neurokinin A (0.3 and 1 microgram) and senktide (0.003 and 0.03 microgram) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting the scopolamine (1 mg/kg)-induced increase in total arm entries. Although the effects of neurokinin A (0.3 microgram) on the scopolamine-induced impairment of spontaneous alternation performance were almost completely antagonized by pretreatment with the NK-2 receptor antagonist cyclo (Gln-Trp-Phe-Gly-Leu-Met) (1 microgram), the inhibitory effects of senktide (0.003 microgram) were not influenced by pretreatment with the NK-3 receptor antagonist [Trp7, beta-Ala8]neurokinin A-(4-10). These findings suggest that neurokinin A inhibits the scopolamine-induced impairment of spontaneous alternation performance associated with working memory through the mediation of tachykinin NK-2 receptors, while senktide has some pharmacological action other than its effects on NK-3 receptors.
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PMID:Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice. 890 97

Systemic (IP) and/or intraseptal (IS) administration of scopolamine (SCP) and diazepam (DZP) induce amnesia, whereas IP injection of the neuropeptide substance P (SP) and choline chloride (ChCl) produce memory facilitation. The septohippocampal cholinergic system has been pointed out as a possible site of SCP and DZP-induced amnesia as well as for the mnemonic effects induced by SP and ChCl. We performed a series of experiments in order to investigate the interactions between cholinergic and GABA/benzodiazepine (GABA/BZD) systems with the SPergic system on inhibitory avoidance retention. Male Wistar rats were trained and tested in a step-down inhibitory avoidance task (1.0 mA footshock). Animals received, pre-training, IP (1.0 mg/kg) or IS (1.0 nM/0.5 microl) injection of DZP, SCP (SCP; 1.0 mg/kg - IP or 0.5 microM/0.5 microl--IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 microg/kg--IP or 1.0 nM/0.5 microl--IS), SP 1-7 (167 microg/kg--IP or 1.0 nM/0.5 microl--IS), ChCl (20 mg/kg--IP or 0.3 microM/0.5 microl--IS) or VEH. Rats pretreated with SCP and DZP showed amnesia. Post-trial treatments with SP 1-11, SP 1-7 or ChCl blocked the amnesic effects of SCP and DZP. These findings suggest an interaction between SPergic and cholinergic mechanisms with GABAergic systems in the modulation of inhibitory avoidance retention and that the effects of these treatments are mediated, at least in part, by interactions in the septohippocampal pathway.
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PMID:Scopolamine- and diazepam-induced amnesia are blocked by systemic and intraseptal administration of substance P and choline chloride. 2060 Apr 32