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 present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons.
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PMID:D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior. 248 60

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

The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6-hydroxydopamine (6OHDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (approximately 30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (> 90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.
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PMID:Dopamine, serotonin and tachykinin in self-injurious behavior. 869 81

Prior studies have suggested a common etiology involved in Tourette's syndrome and several comorbid conditions and symptomatology. Reportedly, current medications used in Tourette's syndrome have intolerable side-effects or are ineffective for many patients. After thoroughly researching the literature, I hypothesize that magnesium deficiency may be the central precipitating event and common pathway for the subsequent biochemical effects on substance P, kynurenine, NMDA receptors, and vitamin B6 that may result in the symptomatology of Tourette's syndrome and several reported comorbid conditions. These comorbid conditions and symptomatology include allergy, asthma, autism, attention deficit hyperactivity disorder, obsessive compulsive disorder, coprolalia, copropraxia, anxiety, depression, restless leg syndrome, migraine, self-injurious behavior, autoimmunity, rage, bruxism, seizure, heart arrhythmia, heightened sensitivity to sensory stimuli, and an exaggerated startle response. Common possible environmental and genetic factors are discussed, as well as biochemical mechanisms. Clinical studies to determine the medical efficacy for a comprehensive magnesium treatment option for Tourette's syndrome need to be conducted to make this relatively safe, low side-effect treatment option available to doctors and their patients.
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PMID:The central role of magnesium deficiency in Tourette's syndrome: causal relationships between magnesium deficiency, altered biochemical pathways and symptoms relating to Tourette's syndrome and several reported comorbid conditions. 1186 98

Morning and afternoon salivary substance P and cortisol levels were measured in 26 adults with chronic self-injurious behavior (SIB) and severe developmental disabilities and compared with matched controls without SIB. Chronic SIB was associated with an altered diurnal pattern of salivary substance P relative to matched controls, characterized primarily by lower levels of morning substance P, which were significantly correlated with overall severity of SIB. There was a trend for SIB subjects to exhibit higher levels of cortisol, which was significantly correlated with overall severity of SIB. These results support a model of altered nociception and possible stress-induced analgesia among individuals with developmental disability and chronic SIB.
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PMID:Altered diurnal pattern of salivary substance P in adults with developmental disabilities and chronic self-injury. 1247 63

The purpose of this preliminary study was to examine the morphology and neuropeptide density of epidermal nerve fibers quantified through skin biopsy samples from three adults with neurodevelopmental disorders and chronic self-injurious behavior (SIB) secondary to mental retardation compared with non-SIB normal IQ controls. A cross-sectional design was used with 3mm punch skin biopsies collected from each participant from non-self-injurious body sites and compared with site-matched existing normal control skin samples. The study was conducted at an outpatient clinic. The primary dependent measure for the morphology analyses was the coefficient of variation (CV) to quantify the mean gap length between epidermal nerve fibers for each subject. Visual microscopic examination and quantitative analysis of the microscopy images suggested there were morphological abnormalities (increased CV) in the epidermal nerve fibers among the chronic SIB cases. Substance P (SP) fiber density was increased with 2-3 times as many fibers in SIB subjects as control subjects. Additional empirical work is needed to clarify the relation between sensory innervation of the skin and self-injury to improve assessment and treatment outcomes.
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PMID:Evidence of altered epidermal nerve fiber morphology in adults with self-injurious behavior and neurodevelopmental disorders. 1785 Sep 69

The aim of this preliminary case study series was to investigate epidermal innervation in pediatric patients with significant neurological impairment and self-injurious behavior. We enrolled four pediatric patients with self-injury (two males, two females; mean age 12y, range 9-14y) and used archival specimens from healthy, age-matched children with typical development for comparison purposes. Epidermal nerve fiber density, peptide content, and mast cell degranulation patterns from non-damaged skin were tested between the patients and the comparison group. The male patients with self-injury had significantly increased epidermal nerve fiber densities, increased substance P positive fiber count and extensive mast cell degranulation compared with sex- and age-matched individuals with typical development. Our case series shows for the first time altered peripheral innervation from non-damaged tissue in children with significant self-injury and developmental disability compared with a healthy comparison group. Establishing the role of peripheral nociceptive and immune modulatory neural pathways may offer new treatment avenues for this devastating neurobehavioral disorder.
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PMID:Skin and self-injury: a possible link between peripheral innervation and immune function? 2518 92