UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wealth of evidence suggests that catecholamines (particularly norepinephrine) influence gonadotropin secretion via a direct interaction with the LHRH neurons. Neuropeptides such as neurotensin (NT) and substance P (SP) are likewise implicated in the control of LHRH secretion, based on pharmacological and preliminary anatomical studies. Since sub-populations of LHRH neurons project to areas of the brain other than the median eminence, a detailed analysis of the topography of axonal interactions of catecholamines (CA), substance P and neurotensin with LHRH cells was conducted in adult male mice using dual immunocytochemical techniques. An analysis of the patterns of apparent contact of NT or SP axons on LHRH cells as determined by close apposition of immunoreactive axons to LHRH cells when viewed under a light microscope at high magnification revealed that the density of NT or SP axons was not a reliable index of the degree of contact; in many locations, NT and SP had similar densities yet a greater portion of the LHRH cells appeared contacted by SP than NT. NT axons were in close contact with up to one-third of the LHRH cells. Analysis of the location of these "contacted" cells did not reveal a discrete subnucleus controlled by NT. Rather, the NT-contacted cells were scattered throughout the LHRH cell field. Interactions of LHRH cells with SP axons were likewise uniform throughout most of the LHRH cell field, with the exception of the most anterior portion of the field. In the anterior septum, few SP axons appeared to contact LHRH cells. Elsewhere, most of the LHRH cells were in contact with SP axons. For the CAs, the fiber density in the regions of the LHRH cells was uniformly moderate, yet the pattern of cells contacted showed variation across the LHRH cell field, with most of the "contacted" cells located near the OVLT and medial preoptic area. These data suggest that LHRH cells may be differentially regulated by NT, SP and the CAs.
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PMID:Organization of LHRH cells: differential apposition of neurotensin, substance P and catecholamine axons. 241 51

Synaptosomes purified from spinal cord and from different rat brain areas exhibit peptide hydrolase activity, cleaving substance P (SP), bradykinin, THRH, LHRH, and neurotensin. The lowest activity for all the peptides tested was found in spinal cord, while the region with the highest degrading activity depended on the substrate: for substance P, it was striatum and cortex; for bradykinin, hypothalamus, and medulla oblongata; for THRH, striatum; for LHRH, midbrain; and for neurotensin, hippocampus. Degradation of substance P takes place at the plasma membrane of synaptosomes. Synaptosome ghosts cleave substance P (pH optimum 7-9, Km-2.5 X 10(-5) M, Vmax-130 nmol . hr-1 . mg protein-1) and also a number of its C-terminal fragments. Effects of the inhibitors show that several different classes of peptidases and proteases are involved in the degradation process. Peptide cleavage represents the probable pathway of synaptosomal inactivation of substance P.
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PMID:Synaptosomal degradation of substance P and some other neuropeptides. 241 81

Angiotensin I converting enzyme (kininase II; ACE) has been described as a peptidyldipeptidase or dipeptidyl carboxypeptidase (EC 3.4.15.1) of the pulmonary endothelial cells, which liberates angiotensin II or inactivates kinins. However, ACE has a much wider distribution and substrate specifity; it is concentrated in human epithelial cells (e.g. brush border of the kidney, placenta, intestine and choroid plexus), neuroepithelial cells (subfornical organ, pallidonigral dendrites, median eminence) and male genital tract (testes, prostate, epididymides, seminal plasma). Its substrates include enkaphalins, the C-terminal extended proenkephalins and a protected chemotactic tripeptide. Recent, mostly in vitro studies with purified ACE, indicate that ACE also cleaves peptides by other than peptidyldipeptidase action. Homogeneous human ACE inactivated substance P in spite of its blocked C-terminus (Met11-NH2) primarily by releasing the C-terminal tripeptide. A blocked C-terminal tripeptide, Arg-Pro-Gly-NH2 was also released from the luteinizing hormone releasing hormone (LHRH). Although ACE shares many properties with carboxypeptidases, it surprisingly cleaves the N-terminal tripeptide greater than Glu1-His2-Trp3 from LHRH. Because human ACE hydrolyzes a variety of peptide hormones, actions of its inhibitors may go well beyond blocking the conversion of angiotensin I.
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PMID:The broad substrate specificity of human angiotensin I converting enzyme. 244 Jun 24

Behavioral experiments tested the idea that the substance P (SP) innervation of the midbrain central gray (MCG) may be involved in the hormonal induction of sexual receptivity in female rats. SP, a SP antiserum or a reported SP antagonist were injected bilaterally into the MCG in ovariectomized, estrogen-treated females, and the lordosis response was recorded at repeated intervals. In the first experiment, three doses of SP (50,500 and 1,000 ng/cannula), a single dose of LHRH (50 ng/cannula) or vehicle were given to separate groups of females. All three doses of SP produced a rapid and long-lasting (3 h) increase in lordosis scores in moderately receptive females in tests with either manual stimulation or male rats. This facilitation was similar in latency, magnitude and duration to that produced by LHRH. In the second experiment, the basic findings of experiment 1 were replicated using blind testing. As no dose-response relation was established in experiment 1, a lower dose of SP (10 ng/cannula) was used in addition to doses of 50 and 500 ng/cannula also used in experiment 1. All three doses produced similar long-lasting increases in lordosis scores as in experiment 1. MCG injections of SP also increased lordosis scores in a second series of tests using manual stimulation alone. This demonstrates that the SP-induced facilitation does not depend on an interaction between the injections and stimuli delivered only by the male rat, eg., vaginal stimuli or ultrasonic calls. The question of the importance of endogenous SP for receptivity was examined in experiment 2 using MCG injections of a SP antiserum or the SP analogue, (D-Pro2, D-Trp7,9)-SP, which has been reported to block the excitation of locus coeruleus neurons by SP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Facilitation of lordosis by injection of substance P into the midbrain central gray. 244 8

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.
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PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. (3H)-AVP was found to bind to a single class of sites with high affinity (Kd = 2.20 +/- 0.18 nM) and low capacity (Bmax = 17.4 +/- 1.8 fmol/10(6) Leydig cells). Binding displacements with specific selective analogs of AVP indicated the presence of V1 subtype receptors on Leydig cells. The ability of AVP to displace (3H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace (3H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells (P less than 0.001). This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation (P less than 0.01). AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation (P less than 0.001). This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels. We conclude from these data that AVP is capable of modulating steroidogenesis in Leydig cells through specific and functionally V1 receptor subtype and postulate that this effect may be part of an intratesticular paracrine/autocrine control mechanism.
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PMID:Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor. 245 54

Antagonists of the putative peptide neurotransmitter substance P have been found to produce pronounced cardiovascular effects when administered into the spinal subarachnoid space. These previous studies have not, however, provided any direct evidence that these effects result from interaction with substance P receptors. The present study was designed to characterize the modification of cardiovascular function resulting from administration of these compounds, and evaluate their effects on the integrity of spinal cord function. Intrathecal administration of two substance P antagonists produced a depressor response accompanied by a reduction of hindquarter vascular resistance. Following administration of a substance P antagonist, the integrated cardiovascular responses to electrical stimulation of the renal afferent nerves and ventrolateral medulla were markedly attenuated. Intrathecal administration to conscious rats of three substance P antagonists led to a variety of sensory and motor dysfunctions, including loss of spontaneous motor function, responsiveness to mechanical and thermal stimuli, and bladder function. No such effects were produced by administration of substance P, luteinizing hormone releasing hormone (LHRH), or LHRH antagonist. These effects from administration of a substance P antagonist were associated with a dose-dependent necrosis of spinal cord tissue. The necrosis may be secondary to ischemia since pretreatment with the vasodilator adenosine significantly delayed or blocked the sensory and motor dysfunctions. This conclusion was supported by the demonstration that cerebrovascular smooth muscle (pial vessels) was constricted by a SP antagonist. Taken together, these data suggest that substance P antagonists appear to non-specifically block transmission in the spinal cord, by mechanisms which may involve reduction of blood flow to the spinal cord.
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PMID:Autonomic, sensory, and motor dysfunction following intrathecal administration of three substance P antagonists. 245 43

Light microscopic double immunocytochemical stainings, performed on sea bass hypothalamo-hypophysial sections, revealed the projection of different neuropeptide-immunoreactive neurons innervating the hormone-producing cell populations in the pituitary gland. In the rostral pars distalis (PD) the ACTH cells were found in close proximity to fibers immunoreactive for somatostatin (SRIF), growth hormone-releasing hormone (GRF), corticotropin-releasing hormone (CRF), vasotocin (VT), isotocin (IT), substance P (SP), neurotensin, and galanin (GAL), while the PRL cell zone seemed only innervated by nerve fibers immunopositive for GAL. In the proximal PD, fibers immunoreactive for SRIF, GRF, VT, IT, cholecystokinin, SP, neuropeptide Y, and GAL formed a close relationship with the growth hormone cells. The gonadotrophs were observed near nerve fibers immunostained for gonadotropin-releasing hormone, IT, and less obviously GRF and VT, while fibers positive for GRF, CRF, VT, IT, SP, and GAL penetrated between and formed a close association with the thyrotrophs. In the pars intermedia the MSH cells and the PAS-positive (PAS+) cells seemed both innervated by separate nerve fibers immunoreactive for GRF, CRF, melanin concentrating hormone, VT, IT, and SP. All these results suggest a functional role of the neuropeptides in the adenohypophysis of the sea bass, possibly in the synthesis and/or release of hypophysial hormones from the different cell types.
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PMID:Immunocytochemical demonstration of close relationships between neuropeptidergic nerve fibers and hormone-producing cell types in the adenohypophysis of the sea bass (Dicentrarchus labrax). 246 54

These experiments further define the organization of peptidergic pathways in the paravertebral sympathetic system of the bullfrog. Populations of axons and synaptic boutons in sympathetic ganglia 9 and 10 were found to express calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) and substance P-like immunoreactivity (SP-IR). CGRP-IR is present in fibers that run through the ganglia and in boutons that make contact with almost half of the principal neurons. SP-IR is also present in fibers within the ganglia and in a rare class of synaptic boutons that are found on less than 1% of the principal neurons. Both forms of immunoreactivity are coexpressed in some nerve fibers and in the rare synaptic boutons that contain SP-IR. Neuropeptide Y-like immunoreactivity (NPY-IR), a marker for C-type postganglionic neurons, was used to identify the postsynaptic targets of boutons containing CGRP-IR and SP-IR. Ninety-five percent of the ganglion cells contacted by CGRP-IR boutons were negative for NPY-IR and are therefore likely to be B-type postganglionic neurons. Similarly, 100% of the ganglion cells contacted by boutons containing SP-IR were negative for NPY-IR. Lesions of the sympathetic chain demonstrated that synaptic boutons containing CGRP-IR arise from neurons whose axons enter the chain rostral to ganglion 7. Cutting the chain between ganglia 8 and 9 eliminates all preganglionic B and C inputs to ganglia 9 and 10. The destruction of the preganglionic C pathway by this lesion was verified by staining ganglia 9 and 10 for luteinizing hormone releasing hormone (LHRH). This lesion also eliminated boutons containing CGRP-IR and drastically reduced the number of ganglionic fibers that stained for CGRP-IR and SP-IR. By contrast, cutting the sympathetic chain between ganglia 6 and 7 spared LHRH-IR in the preganglionic C pathway but still eliminated the boutons that normally express CGRP-IR and reduced the amount of staining for SP-IR. CGRP-IR in the sympathetic ganglia arises from preganglionic and sensory neurons whereas ganglionic SP-IR is purely sensory in origin. In the spinal cord, the preganglionic B and C neurons that innervate ganglia 9 and 10 are located in different segments. In segments that contain preganglionic B cells, but not those that contain C cells, there were 243 +/- 37 (mean +/- SD) neurons in the intermediolateral cell column that express CGRP-IR. However, no cell bodies containing SP-IR were found in this region of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Preganglionic and sensory origins of calcitonin gene-related peptide-like and substance P-like immunoreactivities in bullfrog sympathetic ganglia. 247 76

The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. Active phorbol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.
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PMID:Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. 248 99

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