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)

Immunoreactivity for the neurofilament protein triplet was investigated in neurons of the dorsal root ganglia of the guinea-pig by using a battery of antibodies. In unfixed tissue, nearly all neurons in these ganglia demonstrated some degree of neurofilament protein triplet immunoreactivity. Large neurons generally displayed intense immunoreactivity, whereas most small to medium-sized neurons showed faint to moderate immunoreactivity. Double-labelling immunofluorescence demonstrated that most antibodies to the individual subunits of the neurofilament protein triplet had the same distribution and intensity of labelling in sensory neurons. Increasing durations of tissue fixation in aldehyde solutions selectively diminished neurofilament protein triplet immunoreactivity in small to medium-sized neurons. Double-labelling with neurofilament protein triplet antibodies in combination with antibodies to other neuronal markers, such as neuron-specific enolase, substance P and tyrosine hydroxylase, showed that tissue processing conditions affect the degree of co-localization of immunoreactivity to the neurofilament protein triplet and to these other neuronal markers. These results indicate that, with a judicious manipulation of the duration of tissue fixation, neurofilament protein triplet immunoreactivity can be used in combination with other neuronal markers to distinguish groups of neurons according to their size and chemical coding.
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PMID:Neurofilament protein triplet immunoreactivity in the dorsal root ganglia of the guinea-pig. 171 54

The mudpuppy cardiac ganglion contains 2 neuron types: large parasympathetic postganglionic projection neurons and smaller intrinsic neurons originally described by McMahan and Purves (1976) as intensely fluorescent (SIF) cells. The function of these SIF cells, present in the mudpuppy cardiac ganglion, is unknown. Further, direct application of catecholamines, which are thought to be contained in SIF cells, to the parasympathetic postganglionic cells has no effect (Hartzell et al., 1977). As SIF cells in other ganglion preparations recently have been shown to contain putative transmitter substances in addition to catecholamines, immunocytochemical experiments were conducted to test for the presence of additional transmitter substances in the SIF cells within the cardiac ganglion. Whole-mount septal preparations were dissected from Necturus maculosus and processed for indirect immunocytochemistry. The results indicated that many of these intrinsic neurons contained 5-HT or a substance P-like peptide, or both. Many small intrinsic neurons which contain either substance P or 5-HT were also positive for aqueous-aldehyde-induced fluorescence, indicating the presence of a catecholamine. Finally, some of these cells appeared to contain all 3: a catecholamine, 5-HT, and a substance P-like peptide.
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PMID:Catecholamine, serotonin, and substance P-like peptide containing intrinsic neurons in the mudpuppy parasympathetic cardiac ganglion. 242 25

Although a well-developed plexus of nerves and ganglia is known to be present in the wall of the gallbladder, little has previously been learned about the function or organization of this innervation. The current study was undertaken in order to evaluate the hypothesis that the ganglionated plexus of the gallbladder is analogous to elements of the enteric nervous system (ENS). The ganglionated plexus of the gallbladder was found to resemble closely the submucosal plexus of the small intestine in its organization into two irregular anastomosing and interwoven networks of ganglia, in the numbers of neurons per ganglion, and in the manifestation of histochemically demonstrable acetylcholinesterase activity in virtually all ganglion cells. In common with enteric ganglia, laminin immunoreactivity was observed to be excluded from the interiors of gallbladder ganglia, which were surrounded by a periganglionic laminin-immunoreactive sheath. As in the submucosal plexus, intrinsic substance P-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive neurons were seen in the ganglionated plexus of the gallbladder. Extrinsic nerves in the gallbladder that degenerated following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and which contained NPY, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) immunoreactivities, formed a perivascular plexus closely associated with blood vessels. Endogenous catecholamines could also be demonstrated in these perivascular nerves by aldehyde-induced histofluorescence. In addition to perivascular nerves, paravascular nerve bundles were observed that were loosely associated with vessels, did not degenerate following administration of 6-OHDA, and contained NPY immunoreactivity. Other paravascular nerves, probably visceral sensory axons, coexpressed substance P and calcitonin-gene-related peptide (CGRP) immunoreactivities. The ganglionated plexus of the gallbladder resembled enteric ganglia in having intrinsic 5-hydroxytryptamine (5-HT)-immunoreactive cells and highly varicose nerve fibers. The 5-HT-immunoreactive gallbladder axons were, like those of the gut, resistant to 6-OHDA, and separate from fibers that expressed TH immunoreactivity. Differences between the ganglionated plexus of the gallbladder and enteric ganglia of the small intestine included in the gallbladder are 1) the presence of TH-immunoreactive cells that contain an endogenous catecholamine, but not DBH; 2) DBH-immunoreactive neurons, some of which coexpress substance P immunoreactivity, but which contain neither a catecholamine nor TH immunoreactivity; 3) an apparent absence of CGRP-immunoreactive cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structure, afferent innervation, and transmitter content of ganglia of the guinea pig gallbladder: relationship to the enteric nervous system. 256 71

There are numerous aldehyde fuchsin (AF)-positive, neurosecretory cells of medium size (A cells) and a small number of large, AF-negative neurons (B cells) in the cortical layer of the cerebral ganglion. In the subesophageal ganglion, symmetrical groups of AF-positive cells lie ventrally. The peroxidase--antiperoxidase (PAP) method was used for the immunocytochemical study of substance P and ACTH in these ganglia. In addition, the presence of L-enkephalin and alpha endorphin could be confirmed. Using rabbit antibodies to substance P we found small immunoreactive neurons among negative A and B cells in the cerebral ganglion. The processes of these immunoreactive cells could be traced to the subcortical synaptic neuropil. With antibodies to ACTH, activity was visible in perikarya similar in size to A neurons. A part of the nerve terminals of the synaptic zone, some of the B neurons and further several nerve cells of the subesophageal ganglion reacted positively. Successive demonstration of substance P and ACTH on the same section showed that the two materials occurred in different cell types. Using antiopsin antibody in an indirect immunocytochemical test we observed strong reaction in numerous medium-sized perikarya and in nerve fibres of the synaptic zone of the cerebral ganglion, further in some neurons of the subesophageal and abdominal ganglia. In contrast to this result, the photoreceptor cells of the prostomium and cerebral ganglion were negative. Presumably, substance P is present in a perikaryon type hitherto unrecognized while ACTH and antiopsin reactions seem to be located first of all in A cells.
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PMID:Immunocytochemical studies on the central nervous system of the earthworm, Lumbricus terrestris. 616 89

Prolyl endopeptidase cleaves peptide bonds on the carboxyl side of proline residues within a peptide chain. The enzyme readily degrades a number of neuropeptides including substance P, neurotensin, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. The finding that the enzyme is inhibited by benzyloxycarbonyl-prolyl-proline, with a Ki of 50 microM, prompted the synthesis of benzyloxycarbonyl-prolyl-prolinal as a potential transition state analog inhibitor. Rabbit brain prolyl endopeptidase was purified to homogeneity for these studies. The aldehyde was found to be a remarkably potent inhibitor of prolyl endopeptidase with a Ki of 14 nM. This Ki is more than 3000 times lower than that of the corresponding acid or alcohol. By analogy with other transition state inhibitors, it can be assumed that binding of the prolinal residue to the S1 subsite and the formation of a hemiacetal with the active serine of the enzyme greatly contribute to the potency of inhibition. The specificity of the inhibitor is indicated by the finding that a variety of proteases were not affected at concentrations 150 times greater than the Ki for prolyl endopeptidase. The data indicate that benzyloxycarbonyl-prolyl-prolinal is a specific and potent inhibitor of prolyl endopeptidase and that consequently it should be of value in in vivo studies on the physiological role of the enzyme.
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PMID:Inhibition of rabbit brain prolyl endopeptidase by n-benzyloxycarbonyl-prolyl-prolinal, a transition state aldehyde inhibitor. 634 24

This study investigated the cholinesterasic reactivity of catecholamine neurons in the rat hindbrain with the aid of a two-step histochemical procedure. First, catecholamine cells were visualized by their formaldehyde/glutaraldehyde induced specific histofluorescence and then poststained in the same tissue with a thiocholine technique for acetylcholinesterase (AChE). Processing the vibratome-sectioned tissue in phosphate buffer subsequent to initial aldehyde fixation permitted satisfactory preservation of both amine fluorophores and esterasic reactivity. Our results, in both randomly sampled and serially sectioned material, unequivocally establish the presence of AChE in all pontomedullary cell groups emitting catecholamine fluorescence, the majority of which are known to consist of noradrenaline perikarya. Hence in contrast to previous reports the occurrence of AChE in central noradrenaline neurons appears to be generalized. The intensity of histofluorescence and esterasic staining were uncorrelated in most regions. It remains for future study to determine whether AChE in brain catecholamine neurons indicates their cholinoceptivity or subserves the catabolism of other neuromediators such as substance P.
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PMID:Acetylcholinesterase in pontomedullary catecholamine neurons of the adult albino rat. 706 9

Acetaldehyde administered intravenously at various doses (20, 40 and 80 mg/kg) elicits a dose-dependent increase in intratracheal pressure (ITP) and a proportional rise in histamine blood concentration in anaesthetized guinea-pigs. Similar effects were observed in ovalbumin-sensitized guinea-pigs upon aerosol of acetaldehyde (20 mg/ml) which has been administered at the flow rate of 0.1 ml/min for 2 min. Theophylline (CAS 58-55-9) antagonized both the increase of ITP values and the rise of histamine in the blood caused by acetaldehyde given intravenously (ED50 = 5.8 mg/kg i.v.) or by aerosol (ED50 = 4.9 mg/kg i.v.). Furthermore, in animals where combined treatment with pyrilamine (2 mg/kg i.v.) and captopril (2 mg/kg i.v.) resulted in a remarkable potentiation of the bronchoconstrictor response to acetaldehyde (20 mg/kg i.v.), the administration of theophylline (5 mg/kg i.v.) or of the substance P (SP) receptor antagonist, [D-Pro4, D-Trp7.9] SP 4-11 (10 mg/kg i.v.) reduced the augmented action of acetaldehyde on respiratory airways induced by captopril by more than 50%. Moreover, the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) was also associated with a significant increase of extravasation of Evans blue in tracheal tissue. Both these effects of acetaldehyde were inhibited by theophylline (10 mg/kg i.v.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor antagonist (412 micrograms/kg i.v.) reduced (81%; p < 0.001) only the vascular permeability changes caused by acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of theophylline on both bronchoconstriction and plasma extravasation induced by acetaldehyde in guinea-pigs. 751 75

HNE (4-hydroxy-2,3-trans-nonenal), and aldehydic product of lipid peroxidation, has been reported to modulate different functional parameters of human and rat neutrophils (PMNs), such as chemiluminescence, migration and some enzymatic activities, thus exerting effects that varied according to the concentration tested. Experiments were done to evaluate the effects of HNE on superoxide anion (O2-) production from human PMNs, isolated from healthy volunteers. After having tested that HNE by itself was not able to activate the cells, comparisons were made between its effects on PMNs, stimulated by either a single stimulus, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or a combination of stimuli, such as FMLP and the neuropeptide substance P (SP; primed PMNs). In the concentration range tested (10(-12) - 10(-4) M), HNE inhibited FMLP-evoked O2- production with an IC50 of 11.6 +/- 1.5 x 10(-6) M; at concentrations < or = 10(-6) M, HNE enhanced O2- production elicited by FMLP + SP, while higher concentrations were inhibitory. There was a bell-shaped dose-response curve to the enhancing effects of HNE, depending on the incubation time being recorded after only short periods (< or = 5 min) of the exposure of the cells to HNE; this was not shown by structurally-related aldehydes, such as 2-nonenal and nonanal. These results suggest that low concentrations of HNE may participate in the evolution of the inflammatory process, by contributing to the activation of PMNs. The effects of high concentrations of the aldehyde may represent a mechanism which contributes to the regulation of the extent of the inflammatory response.
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PMID:Effect of 4-hydroxynonenal on superoxide anion production from primed human neutrophils. 888 73

Mystixins are synthetic peptides that inhibit plasma leakage after tissue injury. We sought to determine the mechanism of the antileakage effect of mystixins, with particular reference to the formation of endothelial gaps in postcapillary venules. Intravenous administration of mystixin-7, a prototype heptapeptide (p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH2), decreased Evans blue leakage induced by substance P (5 microg/kg i.v.) with an ED50 (95% confidence limits) of 130 (76-211) microg/kg in trachea and 52 (27-100) microg/kg in skin of anesthetized F344 rats. Leakage was decreased without a reduction in the number or size of endothelial gaps, visualized by silver deposits after silver nitrate staining. The number of silver deposits per tracheal endothelial cell was 11.4 +/- 0.2 (mean +/- S.E.) after vehicle pretreatment vs. 13.0 +/- 0.8 after mystixin-7 pretreatment (100 microg/kg i.v.). Silver deposit diameter was unchanged at 1.4 +/- 0.1 micron. Mean arterial blood pressure dropped by a maximum of 38% from baseline for approximately 10 min after mystixin-7 (100 microg/kg i.v.), then recovered to a plateau at about 13% below baseline. The antileakage effect of mystixin-7 pretreatment in vivo was also demonstrated in aldehyde-fixed vessels perfused in situ with Evans blue at constant flow (skin, 79% reduction; trachea, 49% reduction), which suggests that mystixin can reduce leakage independent of its hypotensive effect. We conclude that the antileakage effect of mystixin does not depend on reducing the number or size of endothelial gaps, but instead could be caused by residual hypotension, which reduces the negative interstitial fluid pressure toward zero, or clogging of endothelial gaps.
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PMID:Anti-inflammatory mystixin peptides inhibit plasma leakage without blocking endothelial gap formation. 945 16

The masking of antigens by aldehyde-containing fixatives or by paraffin embedding procedures is a problem for immunohistochemical studies. Enzymatic digestion, formic acid treatment, microwave heating and autoclave heating have been used to deal with this problem, with microwave heating-based antigen retrieval having become widely used as the method of choice. Microwave heating, however, has the shortcoming that it is difficult to precisely control the heating temperature and it is difficult to apply this method of heating to free-floating sections without damaging the sections. We describe here a simple, reliable and sensitive antigen retrieval method that uses water-bath heating. By this method, the temperature can be precisely controlled to yield effective antigen retrieval with minimal tissue damage in free-floating or paraffin-embedded slide-mounted sections. We found that the best results were obtained with a 30 min incubation in a 10-50 mM sodium citrate solution (pH 8.5-9.0) preheated to and maintained at 80 degrees C in a water-bath, followed by 30 min incubation in 0.3-3% nonfat dry milk to reduce nonspecfic staining. This method is highly effective for both 40 microm free floating sections, slide-mounted cryostat sections and paraffin-embedded slide-mounted sections, and it works well for tissue from diverse species (human, rat, mouse, pigeon, and zebra finch) and for diverse antigens (e.g. enkephalin, substance P, huntingtin, GluR1, GFAP, and ubiquitin). This method was also found to enhance immunolabeling in glutaraldehyde-fixed tissue that had been prepared for ultrastructural examination, without having a deleterious effect on the ultrastructure.
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PMID:A simple and sensitive antigen retrieval method for free-floating and slide-mounted tissue sections. 1063


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