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 neonatal administration of monosodium glutamate (MSG) and castration on hypothalamic and anterior pituitary levels of neurokinin A (NKA) were studied in male and female rats killed at 46 days of age. In male rats treated neonatally with MSG, body, anterior pituitary, testis, ventral prostate, and seminal vesicle weights and serum testosterone levels were significantly lower than in saline-injected controls. Hypothalamic NKA was significantly lower in MSG-treated male rats as compared with the controls, and no apparent changes were recorded in anterior pituitary NKA. Orchidectomy was followed by a significant decrease in hypothalamic NKA in saline controls, but not in MSG-treated rats. In female rats treated with MSG, there was a significant decrease in body, anterior pituitary, and ovarian weights, as compared with saline-injected controls, but no significant differences were observed in uterine weights and serum estradiol levels. Hypothalamic NKA was lower, although not significantly, in MSG-treated rats as compared with the respective controls, and no differences were recorded in anterior pituitary NKA levels. Ovariectomy was followed by a significant decrease in hypothalamic NKA in both MSG-treated and control rats, but NKA in the anterior pituitary was significantly increased after ovariectomy only in saline-treated controls, whereas MSG-treated females failed to show this response. It is concluded that neonatal MSG treatment resulted in a decrease of hypothalamic NKA, which was particularly pronounced in male rats without any significant change in anterior pituitary NKA levels. The response of hypothalamic NKA to castration and the response of anterior pituitary NKA to ovariectomy were also altered in MSG-treated rats; this may reflect a functional block of some neuroendocrine functions of the hypothalamus that resulted from the neuronal lesions induced by MSG.
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PMID:Effects of neonatal administration of monosodium glutamate and castration on neurokinin A levels in the hypothalamus and anterior pituitary of rats. 132 45

Neurotransmitters involved in the central regulation of the autonomic function have, to some extent, been elucidated. Substance P, adrenaline and glutamate neurons originating from the rostral ventrolateral medulla oblongata (VLM) produce a tonic excitation of sympathetic preganglionic neurons. The A1 noradrenaline neurons in the caudal VLM inhibit sympathetic activity by inhibiting neurons in the rostral VLM. In the dorsal medulla, the baroreceptor afferents with substance P converge to the adrenaline-neuropeptide Y (NPY) interneurons located in the dorsal strip of the nucleus tractus solitarius (NTS). These interneurons suppress neuronal activity of the A2 noradrenaline neurons, a vasopressor system, by interacting with alpha 2-adrenergic and NPY receptors. The area postrema, a circumventricular organ devoid of the blood-brain barrier, has access to regulatory information of blood-borne angiotensin II and atrial natriuretic peptide at specific receptors on the neuronal elements. The information is then transmitted to the NTS and dorsal motor nucleus of the vagus. Studies focusing on the physiological and pharmacological profiles of neurotransmitters are expected to enhance our knowledge of the central regulation of the autonomic function.
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PMID:[Central autonomic mechanism and neurotransmitters]. 135 64

Male Wistar rats were subjected to normoxic helium-oxygen mixture under 40 kg/cm2 pressure with subsequent decompression. Their brain's Ach, dopamine, glutamate, substance P were shown to change the turnover rate of the synaptosomal PPI. The findings suggest an unspecific mechanism of action of high tension helium on the neurons. The data obtained shows the high pressure neural syndrome not to be connected with metabolic change of a single neurotransmitter.
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PMID:[The polyphosphoinisitide response evoked by different neuromediators after exposure to a helium-oxygen environment under increased pressure]. 135 79

Neutral endopeptidase 24.11 contains an active site arginine believed to function in substrate binding. This arginine is thought to form an ionic interaction with the COOH-terminal carboxylate of NEP substrates. The functionality of arginine 102 has been investigated by using site-directed mutagenesis to produce mutants in which this residue was converted to a lysine, glycine, glutamine, or glutamate. All of the mutants exhibited essentially full activity as determined with a synthetic peptide amide, glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide. In contrast, activity was detected only with the wild-type enzyme and the lysine mutant using a synthetic substrate containing a free COOH-terminal carboxylate, dansyl-Gly-Trp-Gly. Inhibition studies with the physiologically active peptide substrates substance P, endothelin, and angiotensin I, as well as substance P free acid, [D-Ala2,Leu5]enkephalin, and [D-Ala2,Leu5]enkephalinamide indicated a lack of importance of arginine 102 in substrate binding. With [D-Ala2,Met5]enkephalin and the chemotactic peptide, N-formyl-Met-Leu-Phe, a significant decrease in affinity is observed with the arginine 102 mutants. These results suggest that the contribution of arginine 102 to substrate binding is dependent upon the strength of other subsite interactions. Examination of dipeptides as inhibitors indicates that the nature and orientation of the P'2 residue is important in determining the strength of the interaction of arginine 102 with its substrates.
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PMID:Analysis of the importance of arginine 102 in neutral endopeptidase (enkephalinase) catalysis. 137 21

Serotonergic neurons of the medulla oblongata have been proposed to play a role in the control of sensory, motor and autonomic cells in the spinal cord. Many of these raphe neurons have been shown to contain the undecapeptide substance P as well as the tripeptide thyrotropin-releasing hormone, but evidence for the presence of an excitatory amino acid in these pathways has not yet been documented. In colchicine-treated rats, we have used a combination of retrograde tracing and tri-color immunohistofluorescence techniques to study co-localization of serotonin- and substance P- with glutamate- or aspartate-like immunoreactivities in medullary neurons and the possible spinal projections of these cells. In addition, the distributions of serotonin-, substance P- and glutamate-immunoreactive terminal fields in the dorsal, ventral and lateral horns of the spinal cord were examined with tri-color immunofluorescence in the rat and the primate Macaca fasciculata. In colchicine-treated rats, glutamate- and aspartate-like immunoreactivity was found in practically all serotonin- and substance P-immunoreactive neurons of the B1, B2 and B3 cell groups. Some of these neurons also contained wheat-germ agglutinin conjugated to inactivated horseradish peroxidase and colloidal gold particles retrogradely transported from the spinal cord. In the spinal cords of non-colchicine-treated monkeys and rats, striking co-localization of serotonin, substance P- and glutamate-like immunoreactivities was seen in large boutons, surrounding the dendrites and cell bodies of large alpha motor neurons in the ventral horn. These observations suggest the existence of spinally projecting serotonin/substance P neurons containing excitatory amino acids such as glutamate or aspartate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-, substance P- and glutamate/aspartate-like immunoreactivities in medullo-spinal pathways of rat and primate. 137 53

In this study we have examined structural and neurochemical aspects of retinal and optic nerve development in experimentally growth-retarded fetal guinea pigs following maternal unilateral artery ligation. Eye weight (n = 4) and total retinal area (n = 6) at 62 days gestation (term approximately 66 days) were both relatively spared when expressed as a percentage of body weight but in absolute terms were significantly reduced by 18% (P less than 0.001) and 13% (P less than 0.05) respectively when compared with age-matched controls. The numerical density of neurons in the ganglion cell layer was significantly higher at both 52 days (n = 4) and 62 days (n = 4) in growth-retarded fetuses compared with controls. However, there was no difference between the groups in the total number of neurons in this retinal layer at either age, since retinal areas are reduced in growth retardation. The area of neuronal somata in the ganglion and inner nuclear layers was significantly reduced in growth-retarded fetuses compared with controls. There was a concomitant reduction in the width of the cellular layers in the retina and also in the plexiform (synaptic) and photoreceptor layers. The growth of the outer segments of the photoreceptor layer was particularly affected in peripheral retina. The higher packing density of cells and the reduced growth of the plexiform layers suggests a reduction in the growth of the neuropile in growth-retarded fetuses compared with controls. The radial bundling of ganglion cell axons coursing across the retina to enter the optic nerve head was poorly defined in growth retardation. In addition myelination was delayed in the optic nerve with the numerical density of myelinated axons being significantly reduced (P less than 0.005) in growth-retarded fetuses compared with controls. There was a significant reduction (P less than 0.01) in the number of amacrine cells in the inner plexiform layer expressing Substance P-like immunoreactivity in growth-retarded fetuses compared with controls. Glutamate-like immunoreactivity was most intense in the five laminae of the inner plexiform layer and in the outer plexiform layer and less pronounced in photoreceptors, ganglion cells and their axons. There was no qualitative difference in glutamate immunoreactivity between control and growth-retarded fetuses in any of these structures. Thus we have shown that intrauterine growth retardation has specific effects on the development of the fetal guinea pig retina, reducing the growth of several types of neurons and their processes and affecting the expression of the neuropeptide substance-P in amacrine cells.
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PMID:The structural and neurochemical development of the fetal guinea pig retina and optic nerve in experimental growth retardation. 137 56

The effects of an experimentally induced arthritis on immunoreactivity of putative primary afferents neurotransmitter/neuromodulators were examined. Immunoreactive staining for substance P (SP), calcitonin gene-related peptide (CGRP) and glutamate (Glu) in the monkey dorsal horn was examined following inflammation of one knee joint induced by injection of 5% kaolin and 5% carrageenan. Spinal cords were examined at different time periods after induction of arthritis (2.5, 4, 6 and 8 h). Side to side differences in immunoreactivity were determined by a computer assisted quantitation system. A significant overall decrease in immunoreactivity of the lumbar versus the cervical dorsal horn was found for SP. The decrease for SP showed maximal changes of 68.3% at 4 h and 54.7% at 6 h. Immunoreactivity for CGRP was decreased 31.5% at 8 h and variable at other time points. Immunoreactivity for Glu, showed an ipsilateral increase of 31.4% at 4 h, 33.7% at 6 h, 39.9% at 8 h and a significant effect for lumbar versus cervical. Repetitive peripheral stimulation of the joint was shown to be important for changes in SP and Glu immunoreactivity. Without frequent peripheral stimulation in the early stages of the development of arthritis, SP showed no quantitative side to side differences. Increases in Glu immunoreactivity were present but not as prominent with minimal joint manipulation. These studies suggest that Glu may be involved in the aching pain of inflammation at rest whereas SP, CGRP and Glu may mediate pain induced by joint movement.
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PMID:Neural changes in acute arthritis in monkeys. III. Changes in substance P, calcitonin gene-related peptide and glutamate in the dorsal horn of the spinal cord. 137 98

Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.
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PMID:Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. 138 21

Partial ligation of the sciatic nerve of rats produces hyperalgesia similar to that seen in humans following nerve injury. In this study, we used microdialysis of the spinal cord cerebral spinal fluid (CSF) to test the hypothesis that hyperalgesia is due to an enhanced release of excitatory amino acids (EAA) in response to substance P (SP). Intrathecal SP caused release of aspartate and glutamate in the CSF of rats with partial sciatic ligation at a dose of SP that did not cause release in sham operated animals. Neonatal capsaicin pretreatment blocked SP-induced EAA release in both sham and sciatic ligated animals. Release of EAAs in ligated animals was not significantly different from release in sham-operated animals following higher doses of SP or chemical nociceptive stimulation. These results demonstrate a partial sciatic ligation-induced decrease in the dose of SP required to initiate EAA release in the CSF of the spinal cord, a change which could play an important role in hyperalgesia.
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PMID:Experimental peripheral neuropathy decreases the dose of substance P required to increase excitatory amino acid release in the CSF of the rat spinal cord. 138 86

Amyloid deposits are characteristic of Alzheimer's Disease (AD) and there is growing evidence that amyloid may play an important role in the genesis of this neurodegenerative disease. This review discusses data which suggests that reactive astrocytes and microglia may be a necessary concomitant with amyloid to produce the neuropathology which manifests as AD. Several hypotheses and supporting data for mechanisms by which reactive astrocytes may mediate this neuropathology are presented. These include the possibility that amyloid induces excitotoxicity by interferring with astrocytic glutamate uptake, the possibility that amyloid has this effect via an action on a tachykinin-related receptor and the possibility that proteoglycans released by astrocytes may facilitate the deposition of amyloid plaques. Both symptomatic treatment to enhance cognitive function and treatment to stop the progression of AD are needed. It is hoped that answers to some of the unique questions raised here may provide new insight into the etiology and treatment of AD.
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PMID:Astroglia in Alzheimer's disease. 152 41


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