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)

Five neuropeptides (cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), neurotensin (NT) and substance P (SP)) were measured in 14 brain areas (4 cortical areas, hippocampus, amygdala, 3 striatal areas, 2 thalamic areas and 3 subcortical areas-- septum, substantia innominata and hypothalamus) in 12 brains with neuropathologically confirmed Alzheimer type change and in 13 control brains. Choline acetyltransferase (CAT) activity was assessed in 6 of these areas. Levels of SRIF, but not those of the other peptides, were reduced in several cortical areas in Alzheimer-type dementia (ATD). The distribution and magnitude of the reduction in SRIF were less than that of CAT activity and the temporal cortex was the only region in which there was a significant relationship between CAT and SRIF deficits. Peptide levels were unchanged in hippocampus, amygdala, thalamus, hypothalamus and striatum (except for an increase in SP in the putamen). SRIF levels were increased in substantia innominata in ATD. NT and SRIF were significantly, and VIP and SP non-significantly, reduced in the septum in ATD. Thus, apart from these alterations in the septum, SRIF was the only neuropeptide for which major changes were identified and these did not follow either the pattern of neuropathological change (e.g. in amygdala and hippocampus) or of CAT deficits (e.g. in substantia innominata).
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PMID:Neuropeptides in Alzheimer type dementia. 619 64

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.
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PMID:24-hour variation in content and release of hypothalamic neuropeptides in the rat. 619 15

The influence of neuropeptides on hypothalamic regulation of plasma glucose and pancreatic hormone secretion was studied in anesthetized rats. Neuropeptides were injected directly into the ventromedial hypothalamus (VMH) and the lateral hypothalamic area (LHA) and changes in hepatic venous plasma glucose, insulin, and glucagon concentrations were studied. Injection of bombesin into the VMH resulted in a marked and sustained hyperglycemia in the hepatic venous plasma, which was also observed after injection into the LHA. Microinjection of SRIF into the VMH or LHA caused a decrease in hepatic venous plasma glucose concentration. Injection of neurotensin into the VMH or LHA resulted in a transient release of insulin in the 10-min postinjection samples. In 30- and 60-min postinjection samples, significant increases in glucagon concentrations were observed after substance P injection into the VMH or LHA. No major difference in the plasma glucose, insulin, or glucagon concentrations was observed when VMH and LHA stimulation was compared. These data suggest that glucoregulatory neuropeptides may act on the VMH and LHA, which do not necessarily follow the currently recognized anatomical boundaries.
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PMID:Glucoregulatory effects of intrahypothalamic injections of bombesin and other peptides. 620 99

The release of Met-enkephalin immunoreactive material (ME-IR) from rat spinal slices was measured in vitro. This release increased about 4 fold in response to the addition of K+ ions. K+-evoked release of ME-IR was Ca++ dependent. Veratridine, a depolarizing agent, also stimulated the release of ME-IR. Veratridine-induced ME-IR release was completely prevented by tetrodotoxin (TTX), a Na+ channel blocker. Somatostatin (SRIF) inhibited both basal and K+-evoked release of ME-IR at 10(-7) M. Substance P had a similar effect although higher concentrations were needed. gamma-Aminobutyric acid (GABA) and neurotensin (NT) did not affect the basal release but slightly decreased K+-evoked release at 10(-5) M. Serotonin (5-HT) and noradrenaline (NA), did not affect ME-IR release. These results suggest that some of the neuropeptides present in the spinal cord, especially SP and SRIF, may be potent modulators of ME-IR release at the spinal level.
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PMID:Neuropeptidergic inhibitory regulation of Met-enkephalin immunoreactive material release from rat spinal cord in vitro. 620 87

A non-transformed small-intestinal cell line from the rat (IEC-6) and a human colon cancer cell line (HT 29) were examined for their trophic response to sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also used. Interaction studies were performed on IEC-6 cells by combining EGF or insulin with somatostatin-14. The sensory neuropeptides had no effect either on IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29 cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29 cell growth was inhibited by somatostatin-14 only in the presence of serum with a maximal and significant response at 10(-7) M. Our observations suggest that the sensory neuropeptides do not exert a direct growth-regulatory effect either on IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT 29 cell growth but does not interfere directly with the proliferative effect of serum, EGF, or insulin on IEC-6 cells in this model.
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PMID:Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT 29. 750 79

This study investigated possible sites of contact of nerve fibers containing a range of putative neurotransmitter substances onto neurons in the cat ventral medulla oblongata concerned with autonomic, particularly cardiovascular, regulation. The parasympathetic preganglionic neurons of the nucleus ambiguous (correction of ambiguus) were identified by retrograde horseradish peroxidase tracing from the vagus nerve, and the groups of neurons in the A1 and C1 cell areas and the raphe nucleus by catecholamine enzyme or 5-hydroxytryptamine (5-HT) immunohistochemistry, respectively. Immunoreactive (-ir)nerve fibers and terminals in the vicinity if these neurons were visualized by subjecting the sections to a dual-staining technique using a brown peroxidase-diaminobenzidine reaction product and a blue alkaline phosphatase-Fast blue reaction product. By employing monochrome photography with combinations of blue and orange-red filters, it was possible to discriminate neural elements displaying one or the other reaction product, or colocalization of reaction products. The results revealed the presence of calcitonin gene-related peptide (CGRP) and galanin (GAL)-ir in some motoneurons of the nucleus ambiguus, but not in those innervating the heart via the cardiac vagus nerve. The latter group of parasympathetic efferent neurons were found to be densely innervated by fibers immunoreactive for dopamine beta-hydroxylase (DBH, indicating noradrenaline), glycine (GLY), gamma-aminobutyric acid (GABA), 5-HT, enkephalin (ENK), neuropeptide Y (NPY), substance P (SP), and thyrotropin-releasing hormone (TRH), and, to a lesser extent, by other neuropeptide-ir fibers. The catecholamine cells of the rostral C1 and caudal A1 groups showed a broadly similar pattern of innervation, most noticeably by fibers immunoreactive for DBH, GABA, 5-HT, cholecystokinin (CCK), CGRP, ENK, GAL, NPY, and SP. The 5-HT-ir neurons of the raphe nucleus, some also containing SP, TRH, ENK, or corticotropin-releasing factor (CRF)-ir, were most prominently innervated by terminals containing DBH, GABA, CCK, ENK, NPY, TRH, somatostatin (SRIF), and vasoactive intestinal polypeptide (VIP)-ir. Although the proof that these groups of neurons receive functional synaptic contacts from the immunoreactive fibers awaits further ultrastructural studies, the results do suggest that a wide range of putative transmitters may influence the activity of efferent neurons in the cat medulla controlling autonomic functions.
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PMID:Immunolocalization of putative neurotransmitters innervating autonomic regulating neurons (correction of neurones) of cat ventral medulla. 763 97

We studied inhibition of N-type Ca2+ channels in rat superior cervical ganglion neurons by substance P (SP) and somatostatin-14 (Som). In whole-cell clamp, 70 of 82 acutely dissociated neurons showed inhibition (mean 37%) by 500 nM SP, and 54 of 61 showed inhibition by 240 nM Som (mean 57%). Pertussis toxin (PTX) blocked Som but not SP inhibition; intracellular dialysis with 2 mM GDP-beta-S attenuated inhibition with either peptide. Inhibition was voltage dependent with Som but not with SP. Neurokinin A (1 microM) or B was without effect, implicating NK1 tachykinin receptors. In cell-attached patches with bath-applied drugs, to test for a diffusible messenger, inhibition by SP or Som was only 8%. Thus, SP signaling is voltage independent and PTX insensitive; Som inhibition is voltage dependent and PTX sensitive; and both are membrane delimited.
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PMID:Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways. 767 64

A number of neuroactive peptides including calcitonin gene-related peptide (CGRP), substance P, neurokinin B, opioids, somatostatin (SRIF), galanin, neurotensin and vasoactive intestinal polypeptide (VIP) have been localized in adult rat spinal cord and are considered to participate either directly and/or indirectly in the processing of sensory, motor and autonomic functions. Most of these peptides appear early during development, leading to the suggestion that peptides, in addition to their neurotransmitter/neuromodulator roles, may possibly be involved in the normal growth and maturation of the spinal cord. To provide an anatomical substrate for a better understanding of the possible roles of peptides in the ontogenic development of the cord, we investigated the topographical profile as well as variation in densities of [125I]hCGRP alpha, [125I]substance P/neurokinin-1 (NK-1), [125I]eledoisin/neurokinin-3 (NK-3), [125I]FK 33-824 ([D-Ala2, Me-Phe4, Met(O)ol5]enkephalin)/mu-opioid, [125I]galanin, [125I]T0D8-SRIF14 (an analog of somatostatin); [125I]neurotensin and [125I]VIP binding sites in postnatal and adult rat spinal cord using in vitro quantitative receptor autoradiography. Receptor binding sites recognized by each radioligand are found to be distributed widely during early stages of postnatal development and then to undergo selective modification to attain their adult profile of distribution during the third week of postnatal development. The apparent density of various receptor sites, however, are differently regulated depending on the lamina and the stage of development studied. For example, the density of mu-opioid binding sites, following a peak at postnatal day 4 (P4), declines gradually in almost all regions of the spinal cord with the increasing age of the animal. [125I]substance P/NK-1 binding sites, on the other hand, show very little variation until P14 and then subsequently decrease as the development proceeds. In the adult rat, most of these peptide receptor binding sites are localized in relatively high amounts in the superficial laminae of the dorsal horn. To varying extents, moderate to low density of various peptide receptor binding sites are also found to be present in the ventral horn, intermediolateral cell column and around the central canal. Taken together, these results suggest that each receptor-ligand system is regulated differently during development and may each uniquely be involved in cellular growth, differentiation and in maturation of the normal neural circuits of the spinal cord. Furthermore, the selective localization of various receptor binding sites in adult rat spinal cord over a wide variety of functionally distinct regions reinforces the neurotransmitter/modulator roles of these peptides in sensory, motor and autonomic functions associated with the spinal cord.
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PMID:Neuropeptide receptors in developing and adult rat spinal cord: an in vitro quantitative autoradiography study of calcitonin gene-related peptide, neurokinins, mu-opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors. 778 2

A new metallo-endopeptidase which hydrolyzes atrium natriuretic factor (ANF) has been isolated from human neuroblastoma NB-OK-1 cells. In the present study we show that this metallo-endopeptidase is also present in several other human neuroblastoma cell lines, which include CHP 100, SH-SY5Y, SK-N-BE(2), BE(2)-C and BE(2)M-17. Additionally, we show that this endopeptidase activity is reduced to about 20% of the control during retinoic acid (RA)-induced neuronal differentiation in the RA-sensitive SK-N-BE(2) cells, but not in the RA-resistant BE(2)-M17 cells. This suggests that the inhibition is related to neuronal differentiation and not to a direct effect of 5 microM RA on the enzyme activity. This new enzyme is clearly distinct from neutral endopeptidase (NEP, EC 3.4.24.11) and angiotensin-converting enzyme (ACE,EC 3.4.15.1), since specific inhibitors for these endopeptidases (10 microM phosphoramidon and 1 mM captopril, respectively) had no effect on their activity. However, this enzyme was inhibited 100% by 10 mM o-phenanthroline showing an inhibitory spectrum similar to that of another novel metallo-endopeptidase recently isolated in our laboratory from Xenopus laevis skin secretion. Although the physiological function of this new enzyme in human neuroblastoma cells is not known at the present time, we suggest that it may participate in inactivation of neuropeptides such as atrium natriuretic factor (ANF), substance P, somatostatin-14 and bradykinin in vivo.
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PMID:Human neuroblastoma cells express a novel metallo-endopeptidase activity able to inactivate atrial natriuretic factor: inhibition during retinoic acid-induced differentiation. 813 18

Peptide hormone inactivating endopeptidase (PHIE) is a metalloendopeptidase which was isolated from the skin granular gland secretions of Xenopus laevis [Carvalho, K. M., Joudiou, C., Boussetta, H., Leseney, A. M., & Cohen, P. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 84-88]. This peptidase exhibits a thermolysin-like character and hydrolyzes bonds on the amino terminus of hydrophobic amino acids, performing cleavage of Xaa-Phe, Xaa-Leu, Xaa-Ile, Xaa-Tyr, and Xaa-Trp doublets. When the enzyme recognized a doublet of hydrophobic amino acids such as Phe6-Phe7 of somatostatin-14, Phe7-Phe8 of substance P, Phe4-Leu5 of [Leu5,Arg6]enkephalin, and Tyr4-Ile5 of angiotensin II, cleavage occurred preferentially between these residues. The use of selectively modified carboxy-terminal octapeptide fragments of atrial natriuretic factor (ANF) indicated that the enzyme tolerates as substrates only peptides bearing a P'1 bulky hydrophobic amino acid residue. Although a P'1 hydrophobic residue was a necessary condition, it was found in a number of peptides that all potential cleavage sites were not recognized by the enzyme. These data suggested that this metalloendoprotease requires for its thermolysin-like activity a preferred conformation of the peptide chain. Kinetic results obtained using a series of related substrates derived from biologically active peptides of the atrial natriuretic factor, tachykinin, and enkephalin families indicated the presence of an extended binding site accommodating at least six amino acid residues, in contrast to thermolysin (EC 3.4.24.4) and neutral endopeptidase (NEP; EC 3.4.24.11), which hydrolyze shorter homologous peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the thermolysin-like cleavage of biologically active peptides by Xenopus laevis peptide hormone inactivating enzyme. 850 36


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