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 ventral lateral geniculate nucleus (vLGN) of the thirteen-lined ground squirrel (Citellus tridecemlineatus) is a highly differentiated nucleus that is divisible into five major subdivisions on the basis of retinal projections and cytoarchitecture. To pursue the likelihood that these subdivisions (the dorsal cap, intergeniculate leaflet, external magnocellular lamina, internal magnocellular lamina, and parvicellular segment) correlate with the functional diversity of this complex, the present study examined the neurochemical composition of the vLGN with regard to substances that have previously proved useful in distinguishing functionally distinct subregions within nuclei (i.e., neuropeptide Y (NPY), substance P (SP), leucine and methionine enkephalins, gamma-aminobutyric acid (GABA), cytochrome oxidase (CO), acetylcholinesterase (AChE), and NADPH-diaphorase). The results showed a clear differential neurochemical distribution within the nucleus. Neuropeptide Y immunoreactive perikarya were found predominantly in the intergeniculate leaflet and external magnocellular lamina, with only a few present in the internal magnocellular lamina and dorsal cap, and none observed in the parvicellular segment. NPY+ fibers, however, were present in all divisions except the parvicellular segment. The highest concentration of SP immunoreactive cells was observed in the internal magnocellular lamina, and substantial numbers also were scattered in the external magnocellular lamina and parvicellular segment. SP+ fibers were seen predominantly in the intergeniculate leaflet and the magnocellular laminae. The heaviest concentration of enkephalinergic fibers occurred in the internal magnocellular lamina and dorsal cap, but fibers were also observed in the external magnocellular lamina and intergeniculate leaflet. GABA reactivity was widespread throughout the vLGN, with the dorsal cap and external magnocellular lamina most heavily labeled, followed by the intergeniculate leaflet and the internal magnocellular lamina. Cytochrome oxidase, AChE, and NADPH-diaphorase histochemistry revealed rich reactivity within the dorsal cap, and external and internal magnocellular laminae and paler reactivity in the intergeniculate leaflet and parvicellular segment. The external magnocellular lamina was more reactive for CO and NADPH-diaphorase than AChE, while the internal magnocellular lamina showed the opposite pattern of reactivity. In addition, NADPH-diaphorase reactive cells were present in caudal intergeniculate leaflet and lateral external magnocellular lamina. These local differences in the neurochemical character of the vLGN support its parcellation into multiple subdivisions. Taken in conjunction with the differences in cytoarchitecture and retinal projections, these results suggest substantial functional diversity within the ventral lateral geniculate complex.
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PMID:Immunohistochemical organization of the ventral lateral geniculate nucleus in the ground squirrel. 137 67

This study describes the synthesis and effects of the first antagonist to the widely distributed neuropeptide, galanin, which inhibits the secretion of insulin. The first galanin antagonist is a 20-amino acid-long chimeric peptide of the composition galanin-(1-12)-Pro-substance P-(5-11) amide: Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-Gln-Gln-Phe-Phe-Gly- Leu-Met amide. The peptide dose dependently (IC50 = 1.0 nM) antagonizes the galanin-mediated inhibition of the glucose-induced insulin secretion from mouse pancreatic islets. The antagonist was also found to displace 125I-monoiodo-[Tyr26]galanin from membranes of the insulin producing Rin m 5F cells with an IC50 value of less than 0.1 nM. The antagonist is named galantide.
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PMID:The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion. 137 72

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

An extract of the brain of the rainbow trout, Oncorhynchus mykiss contained high concentrations of both neurokinin A-like immunoreactivity (corresponding to 90 pmol mammalian neurokinin A/g wet tissue) and substance-P-like immunoreactivity (corresponding to 50 pmol mammalian substance P/g wet tissue) measured by radioimmunoassay using antisera directed against the C-terminal regions of the mammalian peptides. In contrast, an extract of the Atlantic cod. Gadus morhua contained only neurokinin-A-like immunoreactivity (151 pmol/g). This apparent paradox was resolved by determination of the primary structures of the fish tachykinins. Trout substance P (Lys-Pro-Arg-Pro-His-Gln-Phe-Phe-Gly-Leu-MetNH2) has the same amino acid sequence in its C-terminal region as that in the corresponding region of mammalian substance P. Cod substance P (Lys-Pro-Arg-Pro-Gln-Gln-Phe-Ile-Gly-Leu-MetNH2), however, contains a substitution at position 8 (Phe----Ile) that abolishes reactivity with the antiserum to substance P but permits reactivity with the antiserum to neurokinin A. The amino acid sequence of cod and trout neurokinin A is the same (His-Lys-Ile-Asn-Ser-Phe-Val-Gly-Leu-MetNH2) and shows two substitutions (Thr3----Ile and Asp4----Asn) compared with mammalian neurokinin A. The data indicate that nervous tissue of teleost fish contain tachykinins that are analogous to the peptides found in mammalian tissues.
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PMID:Substance-P-related and neurokinin-A-related peptides from the brain of the cod and trout. 137 87

Immunohistochemical techniques were used to study the adrenal organs of the anuran species Rana esculenta, Caldula pulchra and Bufo marinus with respect to the distribution and coexistence of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), Leu-enkephalin (Leu-ENK). Met-enkephalin-Arg-Phe (MEAP) and dynorphin A 1-17 (DYN). Antisera against enzymes involved in catecholamine synthesis, i.e., dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), were used for the identification of chromaffin cells. ANP-immunoreactive (-IR) cells occurred in high densities (30%-70% of the total cell population) in all species investigated. In C. pulchra and B. marinus, BNP-IR cells constituted a population of non-DBH-IR and non-TH-IR cells that were different from the ANP-IR cells. A large proportion of the adrenal cells (10%-55%) were immunoreactive to Leu-ENK, and a minority (2%-5%) showed MEAP-immunoreactivity. DYN-immunoreactivity was not observed. The anurans studied exhibited small numbers of SP-IR, CGRP-IR and NPY-IR cells. Immunoreactivities for ANP + Leu-ENK and Leu-ENK + MEAP were shown to coexist. In C. pulchra and B. marinus, immunoreactions for ANP + NPY, ANP+SP and SP + CGRP were also colocalized. Except for DYN, all neurohormonal peptides also occurred in intra-adrenal nerve fibers. SP-IR fibers also displayed CGRP-immunoreactivity and some Leu-ENK-IR fibers contained MEAP-immunoreactivity. In C. pulchra, NPY-IR fibers were found that also showed ANP-immunoreactivity.
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PMID:Distribution patterns and coexistence of neurohormonal peptides (ANP, BNP, NPY, SP, CGRP, enkephalins) in chromaffin cells and nerve fibers of the anuran adrenal organ. 137 3

The present study was undertaken to quantify selected neuropeptides (thyrotropin releasing hormone, substance P, methionine and leucine enkephalin) in the cervical spinal cord and other regions of the central nervous system of Wobbler mice by radioimmunoassays during several stages of the motoneuron disease compared with age- and sex-matched normal phenotype littermates. In Wobbler spinal cord, thyrotropin releasing hormone is higher early in the disease, whereas in the brainstem it is higher at a later stage. Substance P in spinal cord is also higher late in the disease. Leucine enkephalin levels are greater at all stages in diseased spinal cord and brainstem, but methionine enkephalin increases only late in the disease. Highly significant increases of the peptides (except thyrotropin releasing hormone) appear in hypothalamus and midbrain only late in the motoneuron disease. Regression analyses show that thyrotropin releasing hormone in spinal cord and brainstem decreases normally with age in the control mice and at a faster rate related to the extent of motor impairment in Wobbler mice. Thyrotropin releasing hormone and methionine enkephalin in the Wobbler brainstem correlate (P less than 0.05) with the progress of the motoneuron disease. Methionine enkephalin increases faster in Wobbler brainstem and decreases faster in control spinal cord with age. The increase of leucine enkephalin in the Wobbler spinal cord correlates significantly with age and with the progress of the disease, but leucine enkephalin declines slightly with age in the controls. The changes of substance P in spinal cord and brainstem do not correlate significantly with the progress of the disease. In the hypothalamus, increasing values for substance P in control specimens and enkephalins in Wobbler specimens are significantly correlated with age. However, in the midbrain, higher methionine and leucine enkephalin levels are significantly associated with age only in the control mice. Alterations of neuropeptides in the Wobbler mouse spinal cord and brainstem may result from the degeneration of bulbospinal raphe neurons projecting to the ventral spinal cord, or from primary afferent or interneuronal nerve terminals. The data imply that the neuronal degeneration process in the Wobbler motoneuron disease is not limited to motoneurons. In the spinal cord, the data support our previous hypothesis that neuronal sprouting presynaptic to the motoneurons may account for increased neuropeptide concentrations. Alternatively, synthesis and/or degradation of these peptides may be altered. In addition, it is proposed that enkephalinergic neurons may develop abnormally in Wobbler mice. The early increase of leucine enkephalin in the Wobbler spinal cord possibly indicates its importance in the etiology of the motoneuron disease.
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PMID:Alteration in the levels of thyrotropin releasing hormone, substance P and enkephalins in the spinal cord, brainstem, hypothalamus and midbrain of the Wobbler mouse at different stages of the motoneuron disease. 138 70

The hypothalamo-neurohypophyseal tract is known to contain the classical neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin, methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), and galanin are co-stored with vasopressin and/or oxytocin. Recent immunohistochemical studies have revealed the existence of a low to moderate number of substance P-, vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were distributed throughout the organ, whereas somatostatin-immunoreactive fibers were present in the proximal part of the organ. The positive nerve endings were either large in size resembling classical nerve terminals related to perivascular spaces, or smaller similar to peptidergic fibers as described in the CNS. These results indicate that these neuropeptides may be either co-stored with the classical neurohypophyseal hormones or contained in another system of afferents to the organ. The probably distinct functional roles of these neuropeptides in the physiology of the neurohypophysis are discussed.
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PMID:Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo-neurohypophyseal tract: experimental immunohistochemical studies. 138 83

In order to clarify the mechanism of substance P (SP)-induced cortisol secretion from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent fashion. Although the SP-induced [3H]leucine uptake precedes the cortisol secretion, ACTH was slower in inducing [3H]leucine uptake and cortisol secretion. Protein synthesis inhibitors, actinomycin D and cycloheximide, were potent in inhibiting the SP-induced cortisol secretion. SDS-PAGE analysis, revealed that a 240 kDa protein is newly synthesized in BAC cells in response to SP but not ACTH. It was also indicated that the production of this 240 kDa protein was elicited about 30 min after stimulation by SP. Moreover, A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also caused a rapid [3H]leucine uptake and production of 240 kDa protein. In contrast, dibutyryl cAMP did not induce the synthesis of this 240 kDa protein. Calmidazolium, a calmodulin inhibitor, effectively inhibited not only [3H]leucine uptake but also 240 kDa protein production due to SP. On the other hand, KT-5720, an inhibitor of protein kinase A, had no effect on [3H]leucine uptake or 240 kDa production. Using the [125I]calmodulin-membrane overlay method, it was found that the 240 kDa protein was a newly synthesized calmodulin binding protein. From the present study, it was concluded that the de novo synthesis of this 240 kDa protein may be intimately related to the cortisol secretion in SP-stimulated BAC cells associated with an activation of the Ca-calmodulin pathway.
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PMID:de novo synthesis of calmodulin binding protein in substance P-induced steroidogenesis in bovine adrenocortical cells. 138

Carotid bodies from 15 human fetuses of gestational ages 13-19 weeks were examined by light and electron microscopy. They were also labeled with antisera to methionine- and leucine-enkephalins, substance P, and bombesin. At 13 weeks of gestation most fetal glomic cells formed a homogeneous population but a few could be distinguished by light microscopy as rounded, pale fetal chief cells or elongated, darker fetal sustentacular cells, a distinction that became more certain with increasing gestational age. Electron microscopy confirmed this distinction, in which fetal chief cells contained dense-core vesicles and were partially enfolded by cytoplasmic extensions of fetal sustentacular cells. Immunoreactivity to methionine- and leucine-enkephalins was found at all gestational ages and was confined largely to fetal chief cells. Immunoreactivity to substance P was less specific, and there was no reaction for bombesin. Thus, by as early as the 13th week of gestation the two principal types of cell of the mature human carotid body begin to become recognizable on paraffin-embedded sections stained with hematoxylin and eosin. Furthermore, fetal chief cells can synthesize the peptides found in the adult.
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PMID:Glomic cells and their peptides in the carotid body of the human fetus. 144 90

To probe the specificity of the metalloendoproteinase stromelysin toward peptide substrates, we determined kc/Km values for the stromelysin-catalyzed hydrolyses of peptides whose design was based loosely on the structure of a known SLN substrate, substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2, hydrolysis at Gln-Phe, kc/Km = 1700 M-1 s-1). Several noteworthy points emerge from this study: (i) Catalytic efficiency is dependent on peptide chain length with N-terminal truncation of substance P resulting in more pronounced rate-constant reductions than C-terminal truncation. These results suggest the existence of an extended active site for stromelysin. (ii) Preferences at positions P3, P2, P1, P1', and P2' are for the hydrophobic amino acids Pro, Leu, Ala, Nva, and Trp, respectively. (iii) Investigation of specificity at P3' supports our earlier hypothesis that SLN has a requirement for a hydrogen-bond donor at this position in its substrates. Based on these observations, we designed and had synthesized the fluorogenic substrate N-(2,4-dinitrophenyl)Arg-Pro-Lys-Pro-Leu-Ala-Nva-TrpNH2, whose stromelysin-catalyzed hydrolysis can be monitored continuously (kc/Km = 45,000 M-1 s-1).
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PMID:Substrate specificity of the human matrix metalloproteinase stromelysin and the development of continuous fluorometric assays. 147 98


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