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)

Substance P-like immunoreactive (SP-IR) nerves formed 2 types of relationships with nerve cells in the cardiac ganglia of the monkey (Macaca fascicularis). The first type consisted of varicose SP-IR nerve fibres that ramified throughout the cardiac ganglia, forming a loose network with several nerve cell bodies. The second type consisted of several nerve cell bodies enwrapped by a dense pericellular (basket-like) investment of varicose SP-IR nerve fibres. Numerous SP-IR nerve fibres formed perivascular networks around the walls of the blood vessels within the cardiac ganglia and the muscle. The cardiac muscle cells were also innervated either by an isolated single varicose SP-IR nerve fibre or by complex networks. At the ultrastructural level, the substance P reaction product appeared to be associated with the microtubules and the outer mitochondrial membranes of labelled axons. Substance P reaction product was also localised on the membranes of small agranular vesicles of the labelled axon terminals. The SP-IR axons and axon terminals were closely related to the nerve cell bodies and they occurred either singly or in small groups. Most of the axons were enwrapped by a sheath from the adjacent Schwann cells which often exhibited pseudopodia-like processes. None of the axon terminals was observed to make synaptic contact with the cell bodies. However, a few axoaxonal contacts involving SP-IR and non-SP-IR axon terminals were present, the significance of which is not understood. Several axon terminals lay close to blood vessels, and may modulate the activity of these vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical localisation of substance P-like nerves in the cardiac ganglia of the monkey (Macaca fascicularis). 138 Apr 95

The innervation of the heart of the snake Elaphe obsoleta was examined with peptide immunohistochemistry, glyoxylic acid-induced catecholamine fluorescence, and in vitro physiological preparations. Snakes were anesthetized with Nembutal. Many somatostatin (SOM)-like immunoreactive (LI) axons were observed in the sinus venosus, atria, and ventricle. Cell bodies with SOM-LI were found in the intracardiac nerve trunks of the sinus venosus, the interatrial septum, and the atrioventricular region. The SOM-LI axons and cell bodies were not affected by 6-hydroxy-dopamine and capsaicin. They are probably intrinsic parasympathetic neurons. Adrenergic, neuropeptide Y-LI, substance P-LI, and calcitonin gene-related peptide-LI axons were found in the sinus venosus, atria, and ventricle. In spontaneously beating sinoatrial or electrically driven atrial preparations, applied SOM (6 x 10(-9) M and 6 x 10(-8) M) decreased the force of atrial contraction and/or the rate of beating. The effects of SOM were tachyphylactic. SOM had no effect on the force of contraction of the driven ventricle. Stimulation of the left and right vagus nerves elicited negative chronotropic and inotropic responses followed by poststimulus positive inotropic and chronotropic responses. Atropine abolished the inhibition, and bretylium abolished the excitation. After cholinergic and adrenergic blockade, high-frequency vagal nerve stimulation had no effect on heart rate and the force of contraction. Thus, although there is an extensive distribution of intrinsic SOM-LI neurons in the heart and although applied SOM is a potent inhibitor of rate and force, SOM in the vagal neurons does not appear to act as a direct inhibitory transmitter to the cardiac muscle or pacemaker cells.
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PMID:Somatostatin and innervation of the heart of the snake Elaphe obsoleta. 197 Apr 54

The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.
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PMID:Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons. 241 19

Nerve terminals of human cardiac muscle were studied using an electron microscope. Substance P-, Leu-enkephalin- and vasoactive intestinal polypeptide-like (VIP) immunoreactive nerves were demonstrated by use of the light microscope. In addition, VIP- and substance P-like immunoreactive nerves were localized ultrastructurally by the peroxidase-antiperoxidase-method. Muscle specimens were obtained from right auricula of patients undergoing open-heart surgery. In the nerve fibres and terminals, which were situated close to the blood vessels and cardiac muscle cells several vesicle populations were identified. On the morphological basis the terminals could be tentatively categorized as cholinergic, mixed cholinergic-peptidergic, adrenergic, sensory or baroreceptor type, peptidergic and degenerating nerve endings. Substance P-, Leu-enkephalin- and VIP-like immunoreactive nerves were localized between cardiac muscle cells. Nerve terminals, which showed substance P-immunoreaction were observed also close to blood vessels. In substance P- and VIP-immunoreactive nerve terminals the immunoprecipitation was localized in large dense-cored vesicles of about 120 nm in diameter. It is concluded that the intrinsic control of the human heart is most probably regulated by several transmitter candidates. The peptidergic nerves may exert their modulatory interactions in the nerve bundles where they are situated close to each other but a direct effect on the blood vessels and muscle cells cannot be excluded.
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PMID:Peptidergic innervation of human atrial myocardium: an electron microscopical and immunocytochemical study. 243 6

A correlated biochemical and histochemical study was undertaken to identify and quantify the presence of different biogenic amines and a substance P-like peptide within the parasympathetic cardiac ganglion of the mudpuppy (Necturus maculosus). Tissue extracts of the cardiac septum containing the parasympathetic cardiac ganglia from control animals were found, by high-pressure liquid chromatography, to contain significant amounts of norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-HT. To allow neural elements of extraganglionic origin to degenerate, ganglia were explanted and maintained in organ culture for 8 d. Extracts from these explanted preparations had no detectable level of E, and NE was reduced, whereas DA and 5-HT levels were similar to those of control preparations. The results indicated that some of the neurons intrinsic to the cardiac septum contain DA and 5-HT and that most (greater than 70%) of the E and NE found in this tissue is of extrinsic origin. Histochemistry of control and explanted preparations showed 5-HT-immunoreactive and catecholamine-containing intrinsic neurons. A substance P-like peptide was identified by radioimmune assay in septal extracts. The peptide content diminished by one-third to one-fifth in preparations maintained in organ culture for 8-14 d, suggesting that a significant amount of the substance P-like peptide is derived from extraganglionic sources. Immunocytochemical studies demonstrated the presence of numerous long substance P-immunoreactive fibers coursing across the septum, branching over cardiac muscle fibers, and forming pericellular networks around individual parasympathetic ganglion cells and clusters of ganglion cells. In addition, numerous small intrinsic neurons exhibited immunoreactivity for substance P. Comparison of the substance P-staining patterns in control and explanted ganglia suggests that the majority of the long substance P-immunoreactive fibers innervating the mudpuppy cardiac ganglion cells are not parasympathetic preganglionic fibers. Rather, it is hypothesized that these fibers are processes of primary sensory fibers. The present observations indicate that the mudpuppy cardiac ganglion exhibits a complex organization similar to that of mammalian sympathetic and enteric ganglia.
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PMID:Organization of a vertebrate cardiac ganglion: a correlated biochemical and histochemical study. 243 65

A correlated histochemical and pharmacological study was undertaken to establish the presence, origin, and possible function of nerve fibers containing a galanin-like peptide in the mudpuppy (Necturus maculosus) heart. Whole mount preparations of septum-sinus venosus or atria and sections of ventricular muscle were prepared for immunocytochemistry. Galanin-immunoreactive fibers were found coursing diffusely across the septum-sinus venosus to form complex networks over cardiac muscle strands. Individual atrial muscle strands were densely innervated by galanin-immunoreactive fibers and galanin-immunoreactive fibers were also observed in the epicardial and myocardial layers of the ventricle. Most of the parasympathetic postganglionic neurons in the cardiac ganglion and many of the small intensely fluorescent-like cells exhibited galanin immunoreactivity. Galanin-immunoreactive fibers were present in the nerve trunks connecting clusters of parasympathetic postganglionic neurons. Close associations between galanin-positive fibers and individual parasympathetic postganglionic neurons were also observed. The presence of the galanin-immunoreactive fibers was similar in preparations taken from animals pretreated with 6-hydroxydopamine to that seen in preparations taken from control animals, indicating that the galanin-positive fibers were not sympathetic postganglionic axons. Moreover, the galanin-immunoreactive nerve fibers were separate from fibers containing substance P and/or calcitonin gene-related peptide that have previously been shown to be processes of afferent fibers. In twitch-tension experiments, galanin in the range 1 x 10(-7) to 1 x 10(-6) M caused cardioinhibition of spontaneously beating isolated septal-sinus venosus preparations. Galanin also produced a concentration-dependent (1 x 10(-7) to 1 x 10(-6) M) decrease in the twitch-tension development of electrically stimulated atrial or ventricular preparations. Local application of galanin produced hyperpolarization of cardiac muscle fibers in both isolated septal-sinus venosus preparations and atrial preparations. The response of individual parasympathetic ganglion cells to local application of galanin varied between neurons; some neurons were depolarized whereas others were hyperpolarized. We conclude that a galanin-like peptide is contained in both the parasympathetic postganglionic neurons and small intensely fluorescent-like cells and their processes. Further, we hypothesize that in the case of the parasympathetic postganglionic neurons, the galanin-like peptide may work in conjunction with acetylcholine to regulate cardiac activity.
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PMID:The presence and possible role of a galanin-like peptide in the mudpuppy heart. 247 81

The substrate specificity of calcium-activated neutral protease (CANP) from monkey cardiac muscle was examined with various neuropeptides as substrates. The enzyme required mM order calcium ions for activation and had an enkephalinase activity, hydrolyzing Leu-enkephalin at the 1Tyr-2Gly and 3Gly-4Phe bonds. Furthermore, it showed the tendency to cleave especially the bonds around the paired basic amino acid residues in alpha- and beta-neoendorphins and dynorphin(1-13), while it could not hydrolyze substance P.
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PMID:Degradation of neuropeptides by calcium-activated neutral protease. 632 89

Most if not all intracardiac nerve cell bodies in four species of teleost fish and a primitive air breathing fish contained immunoreactivity (IR) to vasoactive intestinal peptide (VIP). Intracardiac nerve cell bodies contained no other neuropeptide although galanin (GAL)-, substance P (SP)- and calcitonin gene-related peptide (CGRP)-IR were detected in cardiac axons. Varicose VIP-IR axons were observed in close association to the cardiac muscle in the sinus venosus and atrium, but not in the ventricle. Slightly less than half the total number of VIP-IR axons also contained colocalised GAL-IR. A smaller number of varicose axons containing colocalised SP- and CGRP-IR were also present in the sinus venous and atrium. In addition, a subpopulation of CGRP-IR axons present in the sinus venosus and atrium did not contain SP-IR. SP-IR axons lacking CGRP-IR formed boutons around the axon hillock and soma of the majority of VIP-IR nerve cell bodies. Associated with a small number of VIP/-ganglion cells were VIP/- boutons. No neuropeptides were observed in the ventricle of any species of fish studied here. These results suggest that a VIP-like peptide is localised in the cholinergic postganglionic parasympathetic neurons. Associated with some of these neurons are nerve boutons containing either SP alone or VIP alone. In addition, the fish heart is innervated by extrinsic nerve fibres containing: GAL/VIP; CGRP alone; and CGRP/SP.
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PMID:The distribution and colocalization of neuropeptides in fish cardiac neurons. 751 44

Dynorphin and alpha-neoendorphin bind to the kappa subtype of opioid receptors and have been shown to inhibit the release of noradrenaline from cardiac sympathetic axons. The purpose of this study was to elucidate the endogenous localization of dynorphin and alpha-neoendorphin in the guinea pig heart. This goal was achieved by double- and triple-labelling immunofluorescence. Dynorphin- and alpha-neoendorphin-immunoreactive nerve fibers were numerous around coronary blood vessels and among cardiomyocytes. They also contained immunoreactivities to the rate-limiting enzyme of catecholamine synthesis tyrosine hydroxylase and to neuropeptide Y. These fibers disappeared in response to chemical sympathectomy (6-hydroxydopamine treatment). In contrast, substance P/calcitonin gene-related peptide-immunoreactive axons of sensory origin did not contain dynorphin and alpha-neoendorphin immunoreactivities and were unaffected by chemical sympathectomy. The findings demonstrate that immunoreactive dynorphin and alpha-neoendorphin are contained in postganglionic sympathetic nerve fibers innervating coronary blood vessels and cardiac muscle. Therefore, the inhibitory effect of these peptides upon noradrenaline release from the sympathetic terminal may well be an autoinhibitory feedback loop.
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PMID:Sympathetic noradrenergic fibers as the source of immunoreactive alpha-neoendorphin and dynorphin in the guinea pig heart. 770 29

Magnesium(Mg)-deficiency, whether dietary or an effect of a clinical condition such as diabetes, results in a variety of cardiovascular pathologies. Substance P (SP) has been implicated in the induction of cardiac focal inflammatory lesions that occur during Mg-deficiency. Blockade of SP receptors results in a significant reduction in the incidence of lesion formation. In an effort to identify potential endogenous cell populations of the heart, which may play a role in SP-dependent lesion formation, film- and light-microscopic autoradiography were used to map the distribution of specific SP binding sites in frozen sections of the normal rat heart and adjacent great vessels. Binding was assessed with 0.1 nM I-125 Bolton-Hunter labelled SP in the absence (total binding) or presence (non-specific binding) of excess unlabelled SP, prolactin, or L-703,606, a non-peptide antagonist of SP receptors. Film autoradiograms revealed prominent small foci of intense autoradiographic reactions dispersed intermittently around the periphery of the great vessels and coronary arteries, among the interstitial connective tissue of the heart, and along the cusps of the cardiac valves. Excess unlabelled SP caused a significant reduction (97.7% displacement; P < 0.001) in the focal autoradiographic reactions. L-703,606 caused a similar reduction in SP binding (97.3% displacement; P < 0.001), while prolactin had no statistically significant effect on the binding of radiolabelled SP. Light-microscopic autoradiograms revealed that the SP binding sites occurred within clusters of connective tissue cells or in rarely observed parasympathetic ganglia. No evidence was found to suggest the presence of SP receptors on endothelial cells, cardiac muscle fibers, or smooth muscle fibers. The connective tissue cells which bound SP within the heart will likely include types that are susceptible to SP activation and thus may play a role in initiation of the focal inflammation characteristic of Mg-deficiency.
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PMID:Distribution of specific substance P binding sites in the heart and adjacent great vessels of the Wistar white rat. 864 67


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