Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lesions of medial habenular nuclei increased the pain sensitivity, enhanced the analgesic activity of morphine and slightly activated the behavior. The lesion of fasciculus retroflexus, a pathway connecting habenular nuclei with interpeduncular nucleus enhanced the pain sensitivity less markedly, did not change the efficacy of morphine analgesia, but significantly increased the activity of animals. The lesion of interpeduncular nucleus influenced the pain sensitivity to a smallest degree, did not change the analgesic activity of morphine, but dramatically increased the activity of animals. The activation did not resemble the aimless excitation of amphetamine-treated or raphe-lesioned rats, and no signs of increased emotionality or irritability were noted. The results are interpreted as an evidence of habenulo-interpenduncular complex being a part of a system, involved in the regulation of behavioral activity and the sensitivity to the aversive stimuli. These functions are in all probability mediated partly through substance P and met-enkephalin containing neurons, present in these structures.
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PMID:Habenulo-interpeduncular lesions: the effects on pain sensitivity, morphine analgesia and open-field behavior in rats. 390 26

Adult male Fischer-344 rats were dosed sc with 1 or 2.5 mg/kg of triethyl lead chloride (TEL) for 5 consecutive days. One week after the last dose, TEL-exposed rats had decreased Met-enkephalin in the hypothalamus, septum, and frontal cortex, while substance P was decreased in the hippocampus and frontal cortex. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus were not altered by TEL nor were serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the caudate nucleus, hypothalamus, hippocampus, or frontal cortex. In a second experiment, rats were dosed with 1.75 mg/kg sc for 5 days. Subsequent assay of brain tissue indicated that TEL decreased met-enkephalin levels in the septum of rats one and seven days after cessation of dosing; effects on substance P were not observed. TEL-induced decreases in Met-enkephalin in the septum were temporally associated with increased hot plate latencies. One day after cessation of dosing with TEL, concentration of 5-HIAA in the caudate nucleus, hippocampus, frontal cortex, and brain stem, and 5-HT in the hippocampus and brain stem were increased. Biogenic amine concentrations were not affected in any other region or at any other time postdosing. A third experiment indicated that TEL-induced analgesia could be attenuated by 10 mg/kg chlordiazepoxide or 10 mg/kg of naloxone. The present results suggest that TEL-induced analgesia may be due to alterations in emotionality or reactivity to noxious stimuli, which may be associated with the alteration in delta opiate mechanism in the limbic system, such as the change of septal enkephalin neuronal activities.
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PMID:Correlation of neurochemical and behavioral effects of triethyl lead chloride in rats. 619 48

Tachykinins play an important role as peptide modulators in the CNS. Based on the concentration and distribution of the peptides and their receptors, substance P (SP) and its cognate receptor neurokinin 1 (NK1R) seem to play a particularly important role in higher brain functions. They are expressed at high levels in the limbic system, which is the neural basis of emotional responses. Three different lines of evidence from physiological studies support such a role of SP in the regulation of emotionality: (1) stress is often associated with elevated level of SP in animals and humans; (2) systematic and local injections of SP influence anxiety levels in a dose-dependent and site-specific manner; (3) NK1 receptor antagonists show anxiolytic effects in different animal models of anxiety. Although these studies point to the NK1 receptor as a promising target for the pharmacotherapy of anxiety disorders, high affinity antagonists for the human receptors could not be studied in rats or mice due to species differences in the antagonist binding sites. However, studies on anxiety and depression-related behaviors have now been performed in mouse mutants deficient in NK1 receptor or SP and NKA. These genetic studies have shown that anxiety and depression-related phenotypes are profoundly affected by the tachykinin system. For example, NK1R-deficient mice seem to be less prone depression-related behaviors in models of depression, and one study also provided evidence for reduced anxiety levels. Mice deficient in SP and NKA behaved similarly as the NK1R knockouts. In animal models of anxiety they performed like wildtype mice treated with anxiolytic drugs. In behavioral paradigms related to depression they behaved like wildtype animals treated with antidepressants. In summary, the genetic studies clearly show that the SP/NK1 system plays an important role in the modulation of emotional behaviors.
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PMID:Mutagenesis and knockout models: NK1 and substance P. 1659 57

It has been suggested by studies in animals and humans that substance P (SP) and its receptor neurokinin 1 (NK1R) play an important role in the pathology of depression. The pharmacological blockade or genetic deletion of the NK1 receptor, or the substance P coding gene tac1 led to a decreased emotionality and a reduction of depression-related behaviours in different animal models. In order to characterize molecular changes associated with reduced SP-NK1 signalling in animal models of depression, we assessed the regulation of the CRH system. First, tac1(-/-) animals and tac1(+/+) controls were subjected to bulbectomy, which induces physiological and behavioural changes that are relevant to depression. We demonstrate that tac1(-/-) animals, in contrast to tac1(+/+) controls, do not show anhedonia in the saccharine preference test after bulbectomy. Next, we studied expression levels of CRH, the receptors CRHR1 and CRHR2, and the binding protein CRHBP in the cortex and paraventricular nucleus using real-time RT-PCR. Our results show a strong induction of CRH, CRHBP and CRHR1 expression in the cortex of tac1(-/-), but not in tac1(+/+) animals. In the PVN, bulbectomized tac1(-/-) mice showed an elevated expression of CRHR1 and CRHR2. These results show that substance P/NKA is involved in modulating CRH signalling in an animal model of depression.
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PMID:Modulation of the CRH system by substance P/NKA in an animal model of depression. 2043 64