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)

As many putative transmitter substances have been shown to be co-localized in areas of the central nervous system involved in cardiovascular control, we have investigated the possibility that some of these substances may interact in eliciting changes in heart rate and arterial pressure in anesthetized rats. In a first set of experiments, interactions between atrial natriuretic factor and glutamate were investigated by microinjection into the nucleus of the tractus solitarius, the site of termination of baroreceptor fibers of the aortic depressor nerve. In addition, interactions between the transmitter released in the nucleus tractus solitarius by electrical stimulation of the aortic depressor nerve and atrial natriuretic factor microinjected into the nucleus tractus solitarius were investigated. Combined microinjection of atrial natriuretic factor and glutamate into the nucleus tractus solitarius, or stimulation of the aortic depressor nerve combined with atrial natriuretic factor in the nucleus tractus solitarius, elicited decreases in heart rate and arterial pressure which were greater than the responses to either substance or stimulation alone or their algebraic sum. In a second set of experiments, interactions between substance P and acetylcholine were investigated in the intermediolateral nucleus of the spinal cord, the location of sympathetic preganglionic neurons. Furthermore, we investigated the possibility that the cardiovascular responses to microinjection of substance P and acetylcholine into the intermediolateral nucleus could be potentiated by the transmitter released in the intermediolateral nucleus by microinjection of glutamate into the rostral ventrolateral medulla, a region with known sympatho-excitatory function.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardioscience 1991 Sep
PMID:Interaction of putative transmitters in central nervous pathways involved in the control of heart rate and arterial pressure. 168 94

The contribution of C-fiber neuropeptides and excitatory amino acids (EAAs) as central mediators of secondary hyperalgesia was assessed by examining the effects of intrathecal (i.t.) administration of receptor-selective agonists and antagonists on foot-withdrawal latencies (from 48 degrees C water), both before and after heat injury of the contralateral hindpaw. The hyperalgesia which develops in the hindpaw contralateral to a heat injury, could be reproduced in uninjured rats following i.t. injection of substance P, neurokinin A and N-methyl-D-aspartate (NMDA) but not following calcitonin gene related peptide (CGRP), neurokinin B, kainate or (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). Contralateral hyperalgesia was reversed by the substance P antagonist Arg1,D-Pro2,D-Phe2-D-His9-substance P, and the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (APV), but not by the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When the limb of the injured hindpaw was pretreated with the C-fiber neurotoxin capsaicin, hyperalgesia in the contralateral hindpaw was unaffected. Furthermore, prior to injury, the capsaicin pretreatment itself produced hyperalgesia in the contralateral hindpaw. The results give support for a contribution of both C-fiber neuropeptides and EAAs to central nervous system plasticity and secondary hyperalgesia following heat injury.
Neurosci Lett 1991 Sep 30
PMID:Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids. 168 78

The distribution in the bowel wall of vasoactive intestinal polypeptide-, neuropeptide Y-, and substance P-containing nerve cell bodies and nerve fibers has been described in human sigmoid colon by immunohistochemical examination. In patients with chronic idiopathic constipation, diverticular disease, and in controls (of tissue taken from patients with carcinoma, from a site distant from the tumor that appeared macroscopically normal), the concentrations of vasoactive intestinal polypeptide, neuropeptide Y, and substance P have been measured by immunoassay in the following preparations of sigmoid colon: mucosa, whole colonic wall with mucosa dissected away, circular muscle, and taenia coli. In idiopathic constipation, the vasoactive intestinal polypeptide content of the whole wall minus mucosa was reduced when compared with controls (P less than 0.05) but was unaltered in the mucosa, circular muscle, and taenia coli. In diverticular disease, the vasoactive intestinal polypeptide content of the mucosa and whole wall minus the mucosal layer was increased when compared with control tissue (P less than 0.05 and P less than 0.02, respectively) but was unaltered in the circular muscle and taenia coli. Substance P and neuropeptide Y levels in all layers of colonic wall were unaltered in these two diseases. The disturbances in the normal neural content of vasoactive intestinal polypeptide in the bowel wall in idiopathic constipation and diverticular disease may initiate or contribute to the functional changes seen in these disorders.
Gastroenterology 1990 Sep
PMID:Vasoactive intestinal polypeptide levels in sigmoid colon in idiopathic constipation and diverticular disease. 169 28

The involvement of perivascular sensory fibers containing substance P (SP) and calcitonin gene-related peptide (CGRP) in the events occurring in conjunction with subarachnoid hemorrhage (SAH) has been studied in a rat model. Two days after blood injection, the time point at which maximum vasoconstriction is occurring in this model, immunocytochemistry and radioimmunoassay showed a reduction in SP- and CGRP-like immunoreactivity (LI). The quantitative measurements revealed a significant 50% reduction of CGRP-LI and a slight reduction of SP-LI in SAH as compared to controls. This partial reduction in neurotransmitter content (denervation) caused no change in the sensitivity of the rat basilar artery to SP or CGRP as studied using a sensitive in vitro method. However, the maximum relaxant response to CGRP was increased from 52 to 81% (p less than 0.05), while there was no change in the maximum SP-induced relaxations. It is suggested that not only a pre-, but also a postsynaptic modulation of perivascular sensory fibers may occur in experimental SAH.
J Cereb Blood Flow Metab 1990 Sep
PMID:Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage. 169 81

Commercially available and affinity-purified butyrylcholinesterases isolated from human serum were examined for their esterasic activity and their ability to hydrolyze various neuropeptides, including neurotensin, substance P, and leucine-enkephalin. The three pools that displayed the lowest esterasic activities were shown to hydrolyze neurotensin with the same HPLC degradative pattern. By contrast, noticeable qualitative and quantitative discrepancies were observed when hydrolyses of substance P and leucine-enkephalin by these three butyrylcholinesterase pools were studied. The pool that exhibited the highest esterasic activity appeared to be homogeneously constituted by 90- and 180-kDa protein bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and was totally unable to hydrolyze these three neuropeptides. This suggested that the three other butyrylcholinesterase preparations could be contaminated by exogenous peptidases. This was confirmed by means of three distinct monoclonal antibodies directed toward human serum butyrylcholinesterase. The three IgG-purified fractions precipitated the esterasic activity, whereas they failed to precipitate the neuropeptide-hydrolyzing activities whatever the substrate examined. Altogether, these results demonstrate that peptidases associated with butyrylcholinesterase are contaminating enzymes that cannot be considered as intrinsic activities of this enzyme.
J Neurochem 1990 Sep
PMID:Monoclonal antibodies allow precipitation of esterasic but not peptidasic activities associated with butyrylcholinesterase. 169 18

The neuropeptides substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide are present in normal rat anterior pituitary gland and hypothalamus and can influence the secretion of classical pituitary hormones. We investigated the effects of estrogen manipulation on pituitary and hypothalamic expression of these four peptides by specific RIAs and cDNA probe analysis. Surgical ovariectomy produced a significant rise in the pituitary content of substance P immunoreactivity (IR) (130.2 +/- 4.8 fmol/gland vs. control 29.1 +/- 2.2, P less than 0.001), neuropeptide Y IR (34.9 +/- 3.9 vs. 19.6 +/- 2.0, P less than 0.05) and neurotensin IR (85.1 +/- 8.2 vs. 62.4 +/- 7.2, P less than 0.05), while vasoactive intestinal peptide IR showed a fall (201.2 +/- 18.8 vs. 285.4 +/- 25.9, P less than 0.05). These patterns were reversed with estrogen replacement or high dose estrogen treatment. Changes in peptide content were accompanied by parallel changes in the mRNA for each peptide. Treatment with an antiestrogen (tamoxifen) resulted in no change in substance P, neuropeptide Y, and neurotensin expression, while vasoactive intestinal peptide IR content decreased to below the assay detection limit. Hypothalamic expression of these peptides did not change with any of the treatments. These results indicate that: 1) the control of the pituitary expression of the four peptides under the influence of estrogen occurs predominantly at the level of gene transcription and 2) normalization of the castration induced changes by exogenous estrogen replacement suggests the changes to be mediated by the absence of this steroid. The regulation of the pituitary expression of these peptides by estrogen support the possibility of their having an autocrine or paracrine role.
Endocrinology 1990 Sep
PMID:The regulation of neuropeptide expression in rat anterior pituitary following chronic manipulation of estrogen status: a comparison between substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide. 169 87

The hypothesis that substance P (SP) elicits both direct and indirect responses on the canine proximal colon was tested using two different in vitro preparations. The mucosa contained the muscularis mucosa and the attendant submucosal plexuses whereas the epithelium, being devoid of both, was functionally "nerve-free." Dose-dependent stimulation was noted on both preparations, increases in peak current (microamperes per squared centimeter) as well as charge transfers (millicoulombs per squared centimeter) were monitored. Tetrodotoxin significantly reduced mucosal responses whereas atropine and the H1 antagonists mepyramine and diphenhydramine had only marginal effects. None of these agents affected the responses of the epithelium to SP. Indomethacin significantly reduced responses in both preparations. Removal of Na+ or Cl- or the use of C- channel blockers (9-anthracene carboxylic acid and N-phenylanthranilic acid) produced a significant reduction of SP responses across the epithelium. Thus, SP has both direct and indirect affects on the colon; activation of the cyclooxygenase pathway could be significant.
J Pharmacol Exp Ther 1990 Sep
PMID:Epithelial and mucosal preparations from canine colon: responses to substance P. 169 22

We have previously shown that substance P (SP) regulates sphincter of Oddi (SO) motility in vivo. However, its mechanism of action remains unclear. Our aim was to develop an in vitro model to measure spikeburst (SB) an contractile frequency (CMC) of the SO and to characterize further SP effects. In 16 opossums, SO rings were excised, mounted within a Kreb's tissue bath with bipolar electrodes and force transducers, allowed to equilibrate, and exposed to increasing SP concentrations with washout between each test solution. Spikeburst and CMC frequencies were recorded on a polygraph, quantitated, expressed as differences before and during SP, and statistically analyzed with Student's test. Although SP induced a significant concentration-dependent increase in phasic SB frequency and CMC, the amplitude of concentrations was not affected by SP. A close correlation was found between basal and SP-stimulated SB and CMC, suggesting myoelectric and mechanical coupling. Previous exposure of SO to SP antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP significantly decreased the response to SP. Tetrodotoxin (TTX), did not affect the delta CMC response to SP. In conclusion an in vitro preparation was developed to study the effect of SP on the SO. Substance P increased SB and CMC of the SO in a concentration-dependent fashion, thus acting as a stimulatory peptide. Perfusion of SO rings with SP antagonist had no effect on basal CMC but significantly inhibited the action of SP in a competitive manner. The effect of SP was not altered by TTX. These data suggest that the action of SP on the SO is primarily myogenic.
J Surg Res 1990 Sep
PMID:Substance P stimulates the opossum sphincter of Oddi in vitro. 169 38

Cardiovascular responses to intracerebroventricular (icv) injections of substance P and somatostatin were measured in Long-Evans and Brattleboro rats treated with streptozotocin (STZ) or saline. Substance P icv evoked similar pressor responses and tachycardia in STZ-treated and saline-treated Long-Evans rats, together with signs of behavioral activation (i.e., arousal). As a group, Brattleboro rats did not respond significantly to icv substance P, although some individual rats showed clear cardiovascular and behavioral responses. These findings may indicate a reduced sensitivity to icv substance P in Brattleboro rats but show no differences attributable to STZ treatment. Hence, diminished pressor responses to icv angiotensin II (observed previously) may be specific to sympathoadrenal activation associated with drinking. Somatostatin caused a pressor effect in saline-treated, but not in STZ-treated, Long-Evans rats, which was probably due to arginine vasopressin (AVP)-mediated mechanisms because it was not present in either saline-treated or STZ-treated Brattleboro rats. Both control and STZ-treated Long-Evans rats showed a bradycardic response to somatostatin that was not seen in Brattleboro rats. These results indicate that different AVP-mediated mechanisms might be responsible for the pressor and bradycardic effects of icv somatostatin. It is possible that impairment of central somatostatin-mediated AVP release contributes to the diminished role of AVP in blood pressure recovery following ganglion blockade in STZ-treated rats described previously.
Am J Physiol 1990 Sep
PMID:Central effects of substance P and somatostatin in conscious, streptozotocin-treated rats. 169 38

This study investigates the ability of P388D1 macrophages to synthesize and secrete substance P (SP). Using a monoclonal anti-SP antibody (termed MASP-1) coupled to Sepharose, it was possible to immunoaffinity purify from culture supernates a peptide that was antigenically related to SP. P388D1 macrophage cultured in the presence of 35S-methionine secreted into culture supernates a labelled peptide which could be recognized by MASP-1. Affinity-purified, P388D1-derived SP was shown to be chemically similar to synthetic SP using gel-filtration chromatography and reverse-phase HPLC. In addition, an RIA using a polyclonal, monospecific antibody was used to quantify the amount of secreted SP in cultured supernates. P388D1 macrophages secreted 222 pg SP per 10(8) cells, whereas SP secretion by control thymocyte cultures was not detectable. The functionality of the P388D1-derived SP was also investigated. Since exogenously added SP can increase secretion of an interleukin-1 (IL-1)-like activity in these cells, we questioned whether an anti-SP antibody could remove P388D1-secreted SP from the culture, and in turn reduce cytokine production. By culturing varying dilutions of MASP-1 with P388D1 cells, it was possible to decrease cytokine production by P388D1 cells compared to cultures containing no antibody or with normal mouse immunoglobulin G (IgG). Taken together, these studies demonstrate that macrophage-derived SP may function in an autocrine or paracrine fashion to modulate macrophage function.
Immunology 1990 Sep
PMID:Substance P production by P388D1 macrophages: a possible autocrine function for this neuropeptide. 169 17


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