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)

A unique case of midgut carcinoid with advanced disease, engaging lymph nodes and liver but still accessible to curative surgery, is reported. Besides elevated urinary levels of 5-hydroxyindoleacetic acid, the diagnosis was based on a positive provocation test with pentagastrin, i.e., basally elevated levels of serotonin in peripheral whole blood increased twofold 3 min postinjection related to the appearance of carcinoid symptoms. After removal of primary and secondary lesions in a two-step procedure carcinoid symptoms disappeared completely. Biochemically, urinary excretion of 5-hydroxyindoleacetic acid and serotonin levels in peripheral blood before and during provocation with pentagastrin were both normalized after surgery and have remained so during 27 months of follow-up. Computed tomographies of the abdomen at regular intervals do not indicate recurrent disease. Histologically, the carcinoid lesions displayed a mixed growth pattern and signs of local aggressiveness. Immunocytochemically, the majority of the tumour cells (positive against neuron specific enolase) showed a positive reaction with serotonin antisera. Substance P-like immunoreactivity was also found in a large proportion of these cells.
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PMID:The pentagastrin test as an indicator of a cure in surgically treated patients with advanced carcinoid disease. 245 57

The behavioral effects and the biochemical changes produced following either a single or repeated intrathecal injection respectively, of the insect peptide proctolin (Arg-Tyr-Leu-Pro-Thr-OH) have been compared with the effects of a stable analogue of thyrotrophin-releasing hormone (TRH) in rats. Intrathecal proctolin (1-100 micrograms) did not produce any marked behavioural effects on its own, while intrathecal TRH analogue (RX 77368, 0.5 microgram) administration produced wet-dog shakes and forepaw-licking behaviours. Proctolin (10 micrograms) significantly attenuated the wet-dog shake and forepaw-licking behaviours evoked by intrathecal RX 77368 administration when it was given 30 min before, but not when given in combination with RX 77368. Repeated intrathecal proctolin administration (10 micrograms twice daily for 5 days) significantly reduced the 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid and TRH levels in the ventral, but not in the dorsal, horn of the spinal cord nor in the brainstem, and elevated hypothalamic TRH without affecting plasma free thyroxine levels when compared with values in saline-treated controls. Repeated proctolin injection did not alter substance P levels in any brain region examined, nor did it affect the choline acetyltransferase activity or the calcitonin gene-related peptide-like immunoreactive levels in the ventral horn of the spinal cord, both of which are principally located in motoneurones in this cord region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of intrathecal proctolin administration on the behaviour evoked by the thyrotrophin-releasing hormone (TRH) analogue (RX 77368) and the indoleamine, TRH, substance P and calcitonin gene-related peptide levels and choline acetyltransferase activity in the rat spinal cord. 246 6

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.
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PMID:Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity. 246 28

In an open study of depressed inpatients, the effects of the selective serotonin uptake blocker fluoxetine on 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and N-terminally extended substance P (SP) in cerebrospinal fluid (CSF) were measured. Thirteen unmedicated patients who met the DSM-III criteria for major depressive episode were included, and 9 completed the study. During treatment the 5-HIAA concentration decreased by 46%. The HVA and HMPG concentrations also decreased significantly, but to a lesser degree. The mean level of N-terminally extended SP was unaffected by fluoxetine treatment, but the pretreatment level correlated significantly with the pretreatment level of HMPG. The pretreatment level of HVA was the only biochemically variable that appeared to predict therapeutic outcome. The plasma concentrations of both fluoxetine and its metabolite norfluoxetine increased significantly between 3 and 6 weeks. Plasma and CSF levels of both the parent drug and its active metabolite were correlated.
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PMID:Fluoxetine treatment of depression. Clinical effects, drug concentrations and monoamine metabolites and N-terminally extended substance P in cerebrospinal fluid. 247 12

Autoinhibition of acetylcholine release by the coexisting peptide galanin in the septal afferents to the hippocampus of the rat was examined in tissue slices from the hippocampus. Galanin inhibits the evoked release of the coexisting neurotransmitter, acetylcholine, in the ventral hippocampus, providing an example of autoinhibition of release of a neurotransmitter by one of the coexisting neurotransmitters. The galanin mediated inhibition of the acetylcholine release is a complement to the well known strong cholinergic autoinhibition. The effects of the coexisting galanin and acetylcholine on several second messenger systems were also examined: acetylcholine acting at muscarinic receptors depresses cyclic adenosine 3',5'-monophosphate and stimulates elevation of cyclic guanosine 3',5'-monophosphate levels, whereas neither cyclic adenosine 3',5'-monophosphate nor cyclic guanosine 3',5'-monophosphate levels were affected by galanin (1 microM). Galanin however inhibited partly the muscarinic stimulation of phosphoinositide breakdown, suggesting that inositol phosphate(s) or diacylglycerol may act as second messenger(s) of the galanin action in the hippocampus. The effects of chronic changes in firing rate on the coexisting neurotransmitters in the rat ventral spinal cord containing serotonin, thyrotropin releasing hormone, substance P and substance K were examined. The tissue levels of the coexisting transmitters were studied in rats chronically treated with imipramine (14 days; 2 x 10 mumoles/kg/day) and zimelidine (14 days; 2 x 10 mumoles/kg/day). Upon treatment with zimelidine the tissue levels of the serotonin metabolite 5-hydroxyindoleacetic acid fall by 32% while thyrotropin releasing hormone levels seem to increase 35% and substance P/substance K levels also increase 48 and 72% respectively. Imipramine treatment resulted in similar although less pronounced changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic studies on functional aspects of coexistence. 248 72

A high content of substance P (124 ng/g wet tissue) was demonstrated by radioimmunoassay in lymph node metastases in a patient with bilateral ovarian carcinoid tumours. The plasma substance P level was elevated but urinary 5-hydroxyindoleacetic acid (5-HIAA) was low. It is suggested that, in some carcinoid patients, an elevated plasma substance P level may help diagnosis and follow-up when urinary 5-HIAA is normal.
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PMID:Substance P in ovarian carcinoid. 615 65

The raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover.
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PMID:Serotonin and gamma-aminobutyric acid turnover after injection into the median raphe of substance P and D-ala-met-enkephalin amide. 617 97

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

The effects of chemical thyroidectomy produced by propylthiouracil treatment or hyperthyroidism produced by daily injections of thyroxine on the content of serotonin, its metabolite 5-hydroxyindoleacetic acid and of substance P in discrete brain nuclei of adult rats have been studied. Brain nuclei were removed by punches of frozen brain slices. The serotonin and 5-hydroxyindoleacetic acid contents were measured by high performance liquid chromatography with electrochemical detection while substance P was assayed by radioimmunoassay. The serotonin level was significantly increased in 11 nuclei of the hypothyroid and in 12 nuclei of the hyperthyroid rats. The 5-hydroxyindoleacetic acid levels were higher in 16 nuclei of the hypothyroid and 7 nuclei of the hyperthyroid animals. The state of the thyroid gland in adult rats also affected the substance P system but less consistently than the serotonin pathway. Thus, the substance P content in the brain of propylthiouracil-treated animals increased significantly in 4 nuclei while it decreased in the septum lateralis and the striae terminalis. Following the chronic thyroxine injections, the substance P level was increased in the nucleus caudatus putamen and the tractus diagonalis and was decreased in the area ventralis tegmenti. We previously reported that neonatal thyroidectomy caused a general increase of the substance P and serotonin contents in many brain nuclei of young rats. It appears that the effects of chemical thyroidectomy on mature and immature rat brain are different for the substance P system, suggesting that thyroxine plays an important role in the maturation of substance P-containing neurons.
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PMID:Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats. 619 1

Neonatal hypothyroidism was induced by injection of 131I on the first living day whilst neonatal hyperthyroidism was induced by daily administration of high doses of thyroxine (T4). Following decapitation, segments of the lumbar spinal cord were microdissected by a punch technique. We measured serotonin and 5-hydroxyindoleacetic acid (5-HIAA) contents by high performance liquid chromatography and both substance P and thyrotropin-releasing hormone (TRH) levels by radioimmunoassay. We demonstrated that: (1) neonatal hyperthyroidism decreased substance P and TRH levels in the dorsal and ventral horns respectively, without modifying serotonin and 5-HIAA contents; (2) neonatal hypothyroidism increased the concentration of substance P in dorsal horn, of TRH in ventral horn (confirming our previous work), of serotonin in ventral horn, and of 5-HIAA in both ventral and dorsal horns; (3) T4-replacement therapy abolishes hypothyroid effects on substance P, TRH, and 5-HIAA, but not on 5-HT accumulation; and (4) bovine growth hormone-replacement therapy has no therapeutic action on the hypothyroid-induced accumulation of substance P, TRH, serotonin and 5-HIAA.
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PMID:Influences of both thyroid and bovine growth hormones on substance P, thyrotropin-releasing hormone, serotonin and 5-hydroxyindoleacetic acid contents in the lumbar spinal cord of developing rats. 620 74


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