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)

We have investigated the effect of intravenous injection of cholecystokinin-8 (CCK-8) and other peptides on gastric lesion formation in response to an intragastric perfusion with 25% ethanol in rats anaesthetized with urethane. 2. Intravenous injection of CCK-8 (50-100 nmol kg-1), but not bombesin (1-100 nmol kg-1), calcitonin gene-related peptide (1-50 nmol kg-1), neurokinin A (1 mumol kg-1) or substance P (100 nmol kg-1), induced protection against gastric haemorrhagic lesions produced by ethanol. 3. The CCKA-antagonist L-364,718 (2.45 mumol kg-1, i.v.) increased the lesion index induced by ethanol and reversed the protective effect of CCK-8 (50 nmol kg-1, i.v.). The CCKB-antagonist L-365,260 (5 mumol kg-1, i.v.) and a lower dose of L-364,718 (0.25 mumol kg-1, i.v.) were ineffective. 4. The gastric protective effects afforded by CCK-8 (50 nmol kg-1, i.v.) were not observed in vagotomized-rats and were reduced by capsaicin pretreatment. In capsaicin-pretreated rats there was a worsening of gastric lesions induced by ethanol-perfusion as compared to those observed in vehicle-pretreated rats. 5. These results demonstrate that the mucosal protective effect of CCK-8 involves, at least in part, the activation of CCKA-receptors and is mediated by vagal capsaicin-sensitive fibres.
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PMID:Protection induced by cholecystokinin-8 (CCK-8) in ethanol-induced gastric lesions is mediated via vagal capsaicin-sensitive fibres and CCKA receptors. 204 17

The developmental toxicology of 13 industrial alcohols (methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, tertiary-butanol, 1-pentanol, 1-hexanol, 2-ethyl-1-hexanol, 1-octanol, 1-nonanol, and 1-decanol), and the behavioral teratogenicity of 4 of these alcohols, were assessed in a series of experiments. The results of individual alcohols have been published previously, but the present paper summarizes the results in view of structure-activity relationships among these alcohols. The alcohols were administered by inhalation for 7 hours per day (6 hours/day for 1-decanol) on gestation days 1-19 to groups of approximately 15 pregnant Sprague-Dawley rats. For developmental toxicology evaluations, dams were sacrificed on gestation day 20. Fetuses were serially removed, weighed, sexed, and examined for external malformations. The frequency of visceral malformations and variations was determined in one-half of the fetuses, and the frequency of skeletal deviations was determined in the other half. Behavioral teratology endpoints were investigated in groups of 15 pregnant rats exposed to one of four alcohols (ethanol, 1-propanol, 1-butanol, and tertiary-butanol) and also involved groups of 18 male rats which were exposed to the same concentrations of each alcohol for 6 weeks, and then mated to untreated females. In the behavioral teratology evaluations, all litters were culled to eight pups and fostered to unexposed mothers. Offspring were tested from days 10-90 on a series of behavioral tests designed to evaluate neuromotor integrity, activity levels, learning, and memory. Additionally, brains were removed from 10 offspring per group at 21 days of age, and were dissected into cerebrum, cerebellum, brainstem, and midbrain; these samples were assayed for steady-state levels of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine (serotonin), substance P, B-endorphin, and met-enkephalin. Congenital malformations were noted for methanol, 1-propanol, isopropanol, and 1-butanol, but only at concentrations in excess of 5000 ppm. These concentrations also produced toxicity in the maternal animals; thus, there was little evidence of selective developmental toxicity among the alcohols. Although sporadic behavioral and neurochemical deviations were detected, no consistent pattern of effects was seen for any of the alcohols we tested. It should be noted that alcohols with chain lengths longer than the butyl series could not be generated as vapors at sufficiently high concentrations to produce observable toxicity in the maternal animals. This limits the generality of these findings to the possible developmental effects of these alcohols when taken through other routes of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats. 223 24

Studies employing conditioned operant behavior of squirrel monkeys, rabbits and pigeons have demonstrated that the neuroactive peptides thyrotropin-releasing hormone (TRH), substance P (SP) and neurotensin (NT) produce marked behavioral effects under a wide range of procedures. These compounds appear to be particularly active when given in combination with other drugs. The co-administration of TRH with chlordiazepoxide, pentobarbital and ethanol potentiates the effects of these agents on punished behavior. Under other conditions SP can reverse the effects of chlordiazepoxide, whereas NT enhances the effects of haloperidol. Neither TRH, SP nor NT are behaviorally active at doses that produced significant interactions. These results support the view that neuropeptides exert modulatory effects on various neurotransmitter systems. An understanding of peptide-drug interactions should contribute to the development of new compounds with enhanced psychopharmacological efficacy and minimal side effects.
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PMID:Neuropeptide modulation of the behavioral effects of drugs. 241 53

The plasma concentrations of neuropeptides (neurotensin, substance P, motilin, somatostatin, vasoactive intestinal peptide and gastrin-releasing peptide), the urinary excretion of 5-hydroxyindoleacetic acid and serotonin, and the platelet concentration of serotonin were compared in 133 patients who could be assigned to one of four groups. These groups were as follows: carcinoid tumors present; history of carcinoid tumors; miscellaneous tumors present; and non-tumor diseases. The test with the most sensitivity (i.e., patients with carcinoid tumors labeled positive) and the test with the most specificity (i.e., patients without carcinoid tumors labeled negative) for the presence of carcinoid tumors was determined. Urinary 5-hydroxyindoleacetic acid excretion had a sensitivity of 73 percent and a specificity of 100 percent; the plasma concentration of substance P had a sensitivity of 32 percent and a specificity of 85 percent; and the plasma concentration of neurotensin had a sensitivity of 41 percent and a specificity of 60 percent. Even when basal plasma concentrations of substance P and neurotensin were elevated, there was no additional increase of these neuropeptides prior to ethanol-induced facial flushing. Although measurements of plasma neuropeptide levels may be helpful in occasional patients with carcinoid tumors, it is concluded that measurements of serotonin overproduction--such as 5-hydroxyindoleacetic acid excretion--are of more general value.
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PMID:Role of neuropeptides and serotonin in the diagnosis of carcinoid tumors. 243 80

The concentrations and contents of immunoreactive substance P (SP), neurokinin A (NKA), vasoactive intestinal polypeptide (VIP) and gastrin releasing peptide (GRP) were measured in acid-ethanol extracts of intestine (duodenum-jejunum-ileum) and pancreas of C57BL/KsJ diabetes-obese (db/db) mice, Aston obese-hyperglycaemic (ob/ob) mice, and their respective lean controls. The intestinal concentration of GRP and pancreatic concentrations of VIP and GRP were 36-57% lower in lean Aston mice than lean C57BL/KsJ mice, indicating the influence of genetic background in control mice. Intestinal concentrations of SP and NKA were reduced by 19-33% in the db/db and ob/ob mutants compared with their lean controls, but the intestinal contents of these peptides were normal or greater than normal due to intestinal hypertrophy of the mutant mice. The intestinal VIP concentration was not altered, but the content was increased by 87% and 25% respectively in db/db and ob/ob mice, whereas the intestinal GRP concentration was reduced by 51% in ob/ob mice. Pancreatic concentrations and contents of NKA, VIP and GRP were similar in lean and db/db C57BL/KsJ mice. However, pancreatic concentrations and contents of VIP and GRP were reduced by 51-55% in ob/ob mice compared with their lean controls. The sensitivity of the present assay did not permit accurate determination of the low pancreatic concentrations of SP. The results suggest that the spontaneous ob/ob and db/db syndromes of obesity and diabetes in mice are associated with reduced intestinal concentrations of SP and NKA. The ob/ob mouse also exhibited reductions of intestinal GRP and pancreatic GRP and VIP concentrations. These changes in regulatory peptides may relate to abnormalities of intestinal and possibly pancreatic function in obese and diabetic mutant mice.
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PMID:Substance P, neurokinin A, vasoactive intestinal polypeptide and gastrin releasing peptide in the intestine and pancreas of spontaneously obese-diabetic mice. 243 55

Collection of blood samples in prechilled heparinized tubes, rapid cooling and centrifugation at 4 degrees C were found to be more important than the enzyme inhibitors aprotinin and EDTA in preserving immunoreactive neuropeptide Y. Nine months after storage of plasma in the frozen state at -20 degrees C or -80 degrees C the recovery of NPY was about 50% of the recovery at immediate analysis. Synthetic substance P added to guinea pig plasma at 37 degrees C disappeared almost entirely within 30 seconds as measured by radioimmunoassay while the concentrations of neurokinin A and neuropeptide K decreased only to a minor extent during a 20 min observation period. The total concentration of immunoreactive substance P and neurokinin A in boiled aqueous and acetic acid extracts of rat dorsal spinal cord was on the other hand stable for 72 h at 4 degrees C, 24 h at room temperature and after freezing and thawing three times. However, chromatographic analysis indicated that the immunoreactivity became increasingly more heterogenous in the samples particularily at room temperature. Acid ethanol and Sep Pak extraction of plasma samples resulted in almost 90% recovery of neuropeptide Y, neuropeptide K and calcitonin gene-related peptide while removing crossreacting substances with high molecular weight.
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PMID:Sample handling techniques when analyzing regulatory peptides. 244 Dec 23

An extraction method is described that allows the measurement of 5-hydroxyindoleacetic acid, dopamine, noradrenaline, substance P and thyrotrophin releasing hormone in the same sample of rat or human spinal cord. The substances were extracted using a mixture of 45% ethanol/0.1 M acetic acid and 0.02% sodium metabisulphite. The amines were then measured using high performance liquid chromatography with electrochemical detection and the peptides by radioimmunoassay. The common extraction method makes maximum use of limited postmortem material, reduces assay time and allows study of the interrelationships between the amines and peptides in rat or human spinal cord.
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PMID:Measurement of catecholamines, indoleamines, thyrotrophin releasing hormone and substance P in rat and human spinal cord using a common extraction method. 244 49

Neuronal precursor cells present in dorsal root ganglia (DRG) during early development have been previously shown to differentiate in vitro to neurons, as characterized by morphology, cell surface antigens, and electrophysiological properties (H. Rohrer, S. Henke-Fahle, T. El-Sharkawy, H. D. Lux, and H. Thoenen, 1985, Embo J. 4, 1709-1714). In the present study the conditions necessary for the initial differentiation and long-term survival of these cells were established, and the neurotransmitter phenotype of the newly differentiated neurons was analyzed. Neuronal precursor cells isolated from chick DRG at Embryonic Day 6 (E6) were found to require the presence of a polyornithine substrate coated with either laminin or fibronectin for initial neurite production and long-term survival. Neurons were unable to develop on polyornithine alone or on polyornithine coated with BSA. The survival and neurite outgrowth from neuronal precursor cells was not affected by the presence of nerve growth factor (NGF) during the first 9 hr in culture. NGF also had no effect on the proportion of cells expressing the neuron-specific Q211 antigen. However, after this initial differentiation period the neurons did require the presence of a survival factor. The neurons could be maintained for at least 6 days in culture both in the presence of NGF and in the presence of brain-derived neurotrophic factor (BDNF). At saturating concentrations of both survival factors no additive effects could be observed, indicating a complete overlap of NGF- and BDNF-responsiveness. Although the same proportion of cells survived with either NGF or BDNF during the first 3 days in culture, survival decreased in the presence of BDNF but not in the presence of NGF during the following 3 days in culture. The loss of BDNF responsiveness in vitro was also observed in vivo. After 6 days in culture about 70% of the neurons expressed substance P immunoreactivity, and approximately the same proportion was positive for myelin-associated glycoprotein immunoreactivity. The neurons did not express properties of adrenergic neurons such as tyrosine hydroxylase immunoreactivity or norepinephrine uptake. These findings indicate that the neuronal precursor cells from E6 DRG acquire the same characteristics in vitro as in their normal in vivo environment.
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PMID:Neuronal precursor cells in chick dorsal root ganglia: differentiation and survival in vitro. 245 Jul 97

Substance P (SP) effects on the central mechanisms of escape reaction, elicited by threshold electrical stimulation of the ventromedial hypothalamus were investigated in rabbits pretreated with ethanol (0.5 g/kg). SP (30 micrograms/kg) was demonstrated to normalize in 71.4% of cases the excitability of the ventromedial hypothalamus which was decreased by ethanol and restored in 83.3% of cases the facilitatory effects of the midbrain reticular formation in escape reactions. However, SP was ineffective in the restoration of the inhibitory effects of the dorsal hippocamp on the excitability of the ventromedial hypothalamus that was obvious in intact animals. Partial normalizing effect of SP on escape reaction in rabbits after previous ethanol administration can be accounted for by the fact that both undecapeptide and ethanol are similar in their realization of central effects such as an interaction with the same brain neurotransmitters, interference with neuronal enzyme processes and reactions with opiate receptors.
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PMID:[Substance P and effects of ethanol on the central mechanisms of the escape reaction in rabbits]. 245 83

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.
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PMID:[Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits]. 247 80


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