Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lymphatic vessels conduct lymph fluid, proteins, and potentially antigenic material from the interstitium back to the bloodstream via lymph nodes, where solids are removed by phagocytic cells and recirculating lymphocytes and immunoglobulins are added. Immunostaining for two general neuronal markers, protein gene product 9.5 (PGP 9.5), a cytoplasmic ubiquitin C-terminal hydrolase, and synaptophysin, a calcium-binding four-span integral synaptic vesicle membrane glycoprotein, disclosed an abundant innervation of the large femoral lymphatic vessels in rats. This confirms and extends earlier findings based on nonspecific intravital methylene blue and silver impregnation staining methods. Nerves containing neuropeptide Y, C-flanking peptide of neuropeptide Y, and tyrosine hydroxylase, markers of noradrenergic postganglionic sympathetic fibers, were frequent whereas immunoreactivity to vasoactive intestinal peptide, a neuropeptide present in many cholinergic parasympathetic nerve fibers, was sparse suggesting possible sympathetic and parasympathetic influences. Furthermore, calcitonin gene-related peptide- and substance P-containing fibers were also present in the walls of lymphatic vessels suggesting a possible sensory influence in the coordinated myogenic responses. By comparison to normal light microscopy, confocal microscopy was found useful to trace the perihilar penetration of blood and afferent lymphatic vessels in lymph nodes. PGP 9.5-immunoreactive fibers were found in and around lymph nodes suggesting that there is a neural regulation of lymphoid node function. Because of their distribution, peptide-containing nerves may participate in regulating the capacity of the lymphatic pumping activity, and may possibly exert paracrine effects on lymphocytes.
 ...
PMID:Peptide-containing innervation of rat femoral lymphatic vessels. 160 41

In the lymphatic vessels of man and most animals the nerve fibers are confined to the adventitia. However, immunohistochemical studies suggest that acetylcholinesterase-positive and monoamine-containing fibers reach as far as the endothelium in bovines. The aim of this study was to verify the presence of subendothelial nerve fibers by transmission electron microscopy (TEM) in bovine mesenteric lymphatics and to determine whether typical sensory neurotransmitters such as Substance P (SP) and calcitonin gene related peptide (CGRP) could be detected in these fibers. TEM revealed numerous unmyelinated nerve fibers in the subendothelial connective environment in close association with endothelial cells. Their axons were devoid of Schwann cell sheath on the endothelial side and contained small clear vesicles and large nerve fibers were demonstrated to be SP and CGRP-immunoreactive with mouse monoclonal antibodies against SP and rabbit polyclonal antibodies against CGRP. It is hypothesized that these fibers act as mechanoceptors capable of detecting intraluminal pressure and vessel wall tension variations and of locally releasing SP and CGRP. Since SP, potentiated by CGRP, is known to be a vasoconstrictor in lymphatics, we propose that the contraction of bovine mesenteric lymphatics may also be neurogenic.
 ...
PMID:Subendothelial nerve fibers in bovine mesenteric lymphatics: an ultrastructural and immunohistochemical study. 752

This study examined the distribution of peptidergic nerve fibers in Peyer's patches to determine whether appropriate receptors were present. Vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and receptors for VIP and SP were localized in lymphoid follicles of the cat ileum using a combined indirect horseradish peroxidase and streptavidin-biotin method. The margins of follicles were innervated by nerve fibers containing VIP, SP and CGRP. Nerve fibers were predominantly around lymphatics and high endothelial venules at the edges of follicles. Specific receptors for VIP and SP were present at the margins of follicles and in the lamina propria around crypts. VIP receptors were numerous on T cells within and around high endothelial venules and lymphatic vessels and at the margins of follicles. SP receptors were identified on a small number of T and B cells, granulocytes and macrophages, restricted to the margins of follicles. The defined distribution in ileal lymphoid tissue of nerve fibers containing VIP and SP and the corresponding localization of their appropriate receptors support immunoregulatory roles for neuropeptides in mucosal immunity.
 ...
PMID:Immunohistochemical localization of peptidergic nerve fibers and neuropeptide receptors in Peyer's patches of the cat ileum. 753 34

The submucous neurons, especially those related to the lymphatic vessels, together with their associated synapses, were studied ultrastructurally with respect to their immunoreactivities for 3 types of neuropeptides, namely substance P (SP), vasoactive intestinal peptide (VIP) and somatostatin (SOM). With the antibodies directed against the 3 types of neuropeptides, a variable number of submucous neurons including those contacting the lymphatic vessels were immunostained. Based on the immunoreactivities and synaptic relations with the submucous neurons contacting the lymphatic vessels, at least 4 types of synaptic relations with the submucous neurons contacting the lymphatic vessels, at least 4 types of synaptic configurations were observed: immunopositive terminals with positive neurons, immunopositive terminals with negative neurons, immunonegative terminals with positive neurons and immunonegative terminals with negative neurons. All 4 types of synaptic configurations were observed in SP and VIP-immunostained specimens, with the exception of type 3 which was not encountered in samples immunoreacted for SOM. When the proportions of all 4 types of peptidergic immunopositive terminals contacting the lymphatic vessel-associated neurons were totalled, the value exceeded 100%, suggesting the coexistence of 2 or more neuropeptides in the same terminals. Furthermore, some immunoreactive axon terminals made direct synaptic contacts with positive neurons suggesting the formation of the so-called 'peptide neuron chain'. It is speculated from this study that the submucous neurons receive multiple peptidergic inputs. The various synaptic contacts would imply a complicated reflex pathway in the submucous plexus.
 ...
PMID:Ultrastructural localisation of substance P, vasoactive intestinal peptide and somatostatin immunoreactivities in the submucous plexus of guinea pig ileum. 754 33

A unique group of neurons in the submucous plexus of the gastrointestinal tract in guinea pigs was studied using (1) Nissl staining and an enzyme histochemical technique for acetylcholinesterase (AChE), (2) immunohistochemical methods for the localisation of neuron specific enolase (NSE) and neuropeptides, including vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM), calcitonin gene-related peptide (CGRP), leu-enkephalin (leu-ENK), neuropeptide (NPY) and cholecystokinin (CCK), (3) a fluorescence tracer technique involving the intraperitoneal (i.p.) injection of fluorogold, and (4) normal electron microscopy. The results showed that these neurons were distributed singly or in groups in the submucosa. They were closely adherent to the outer walls of lymphatic vessels, some appearing to protrude into the lumen. Ultrastructurally, only a thin layer of basal lamina and some collagen fibrils intervened between the endothelia of the lymphatic vessels and these neurons. Based on their synaptic contacts and the features of their content of synaptic vesicles, at least 4 types of axon terminal forming synaptic contacts with the 'lymphatic vessel-associated neurons' (LV-AN) were identified. The sources of origin of these terminals remains uncertain although it is speculated that they may be derived from vagal efferents or of intrinsic origin from the neighbouring neurons. All the LV-AN showed AChE and NSE positive reactions, but only a varying number were positive for VIP, SP, SOM, ENK, CGRP, CCK or NPY. The LV-AN were labelled with fluorogold injected i.p.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Studies of the lymphatic vessel-associated neurons in the intestine of the guinea pig. 755 16

The distribution of nerve fibers containing either calcitonin gene-related peptide (CGRP) and substance P (SP) was investigated in rat skin with special reference to their relationship to the lymphatic vessels. These nerve fibers exhibited a similar distribution pattern but the former were more numerous than the latter. In the dermis and subcutaneous layers, thin nerve fibers containing CGRP or SP were in abundance, and were observed running along the blood vessels as well as freely in the tissue. Nerve fibers with these peptides were often located close to lymphatic capillaries, and innervated lymphatic vessels in the subcutaneous layer, reaching smooth muscles of the tunica media. These findings suggest that some CGRP and SP may directly drain into lymphatic vessels when released under noxious stimulation from nerve fibers around the lymphatic vessels. When discharged from nerve fibers in the vicinity of blood vessels, both peptides may also drain into the lymphatic vessels after causing blood vascular dilation and an increase in permeability producing edema. These peptides may then be transported to the draining lymph nodes where they can modulate the functions of the immune system.
 ...
PMID:An examination of the close relationship between lymphatic vessels and nerve fibers containing calcitonin gene-related peptide and substance P in rat skin. 921 40

1. In vitro studies were performed to examine the mechanisms underlying substance P-induced enhancement of constriction rate in guinea-pig mesenteric lymphatic vessels. 2. Substance P caused an endothelium-dependent increase in lymphatic constriction frequency which was first significant at a concentration of 1 nM (115 +/- 3% of control, n = 11) with 1 microM, the highest concentration tested, increasing the rate to 153 +/- 4% of control (n = 9). 3. Repetitive 5 min applications of substance P (1 microM) caused tachyphylaxis with tissue responsiveness tending to decrease (by an average of 23%) and significantly decreasing (by 72%) for application at intervals of 30 and 10 min, respectively. 4. The competitive antagonist of tachykinin receptors, spantide (5 microM) and the specific NK1 receptor antagonist, WIN51708 (10 microM) both prevented the enhancement of constriction rate induced by 1 microM substance P. 5. Endothelial cells loaded with the Ca2+ sensing fluophore, fluo 3/AM did not display a detectable change in [Ca2+]i upon application of 1 microM substance P. 6. Inhibition of nitric oxide synthase by NG nitro-L-arginine (L-NOARG; 100 microM) had no significant effect on the response induced by 1 microM substance P. 7. The enhancement of constriction rate induced by 1 microM substance P was prevented by the cyclooxygenase inhibitor, indomethacin (3 microM), the thromboxane A2 synthase inhibitor, imidazole (50 microM), and the thromboxane A2 receptor antagonist, SQ29548 (0.3 microM). 8. The stable analogue of thromboxane A2, U46619 (0.1 microM) significantly increased the constriction rate of lymphangions with or without endothelium, an effect which was prevented by SQ29548 (0.3 microM). 9. Treatment with pertussis toxin (PTx; 100 ng ml-1) completely abolished the response to 1 microM substance P without inhibiting either the perfusion-induced constriction or the U46619-induced enhancement of constriction rate. 10. Application of the phospholipase A2 inhibitor, antiflammin-1 (1 nM) prevented the enhancement of lymphatic pumping induced by substance P (1 microM), without inhibiting the response to either U46619 (0.1 microM) or acetylcholine (10 microM). 11. The data support the hypothesis that the substance P-induced increase in pumping rate is mediated via the endothelium through NK1 receptors coupled by a PTx sensitive G-protein to phospholipase A2 and resulting in generation of the arachidonic acid metabolite, thromboxane A2 this serving as the diffusible activator.
 ...
PMID:Evidence that the substance P-induced enhancement of pacemaking in lymphatics of the guinea-pig mesentery occurs through endothelial release of thromboxane A2. 928 91

The passive and active length-tension relationships of isolated rat mesenteric lymphatics ( approximately 150 microm ID), and adjacent small arteries ( approximately 240 microm) and veins ( approximately 275 microm) were compared under isometric conditions using a wire myograph. About 60% of the lymphatic vessels developed spontaneous contractions in physiological saline solution at nominal preload. To maximally activate smooth muscle, 145 mM K(+) + 5 x 10(-5) M norepinephrine was used for arteries, and 145 mM K(+) + 1 x 10(-6) M substance P was used for lymphatics and veins. In response, arteries exhibited monotonic force development to a plateau level, whereas lymphatics and veins showed biphasic force development, consisting of a transient force peak followed by partial relaxation to a plateau over approximately 5 min. The passive and the active length-tension curves were similar in shape among all three vessels. However, the maximal active tension of arteries (3.4 +/- 0.42 mN/mm) was significantly greater than peak active tension (0.59 +/- 0.04 mN/mm) or plateau tension (0.20 +/- 0.04 mN/mm) in small veins and greater than peak active tension (0.34 +/- 0.02 mN/mm) or plateau tension (0.21 +/- 0.02 mN/mm) in lymphatics. Maximal active medial wall stress was similar between lymphatics and veins but was approximately fivefold higher in small arteries. For lymphatics, the pressure calculated from the optimal preload was significantly higher than that found previously in isobaric studies of isolated lymphatics, suggesting the capacity to operate at higher than normal pressures for increased responsiveness. Our results represent the first mechanical comparisons of arterial, venous, and lymphatic vessels in the same vasculature.
 ...
PMID:Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation. 1717 74

Substance P (SP) is a neuropeptide associated with sensory innervation of lymphoid tissue and a suspected modulator of lymphatic function in inflammation. Only a few studies have examined the effects of SP on lymphatic contraction, and it is not clear to what extent SP acts directly on the lymphatic muscle and/or endothelium or indirectly through changes in intraluminal filling pressure secondary to increases in capillary permeability/filtration. We tested the effects of SP on the spontaneous contractions of rat isolated mesenteric lymphatic vessels under isometric and isobaric conditions, hypothesizing that low concentrations would stimulate lymphatic pumping by enhancing lymphatic muscle contraction in a manner complementary to the effect of increased preload. Under isometric conditions, SP (10 nM) dramatically enhanced lymphatic chronotropy and inotropy. Unlike guinea pig lymphatics, SP actions were not blocked by cyclooxygenase or PLA(2) inhibition. In the absence of SP, ramp increases in isometric preload resulted in x approximately 1.6 increases in contraction amplitude (Amp) and x approximately 1.7 increases in frequency (Freq). SP increased Freq by x approximately 2.4, Amp by x approximately 1.9, and the Amp-Freq product (AFP) by x approximately 3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH(2)O in the absence of SP decreased Amp by x approximately 0.6 and increased Freq by x approximately 1.8. SP caused a modest increase in Amp, a robust increase in Freq at all pressures, and shifted the AFP-pressure relationship upward and leftward. Therefore, SP has substantial positive inotropic and chronotropic effects on rat lymphatic muscle, improving pump efficiency independent of the effects of preload and broadening of the working range of the lymphatic pump.
 ...
PMID:Modulation of lymphatic muscle contractility by the neuropeptide substance P. 1853 52

We tested the hypothesis that lymphatics would exhibit myogenic constrictions and dilations to intraluminal pressure changes. Collecting lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized for in vitro study. The lymphatic diameter responses to controlled intraluminal pressure steps of different magnitudes were tested in the absence and presence of the inflammatory mediator substance P, which is known to enhance lymphatic contractility. Myogenic constriction, defined as a time-dependent decrease in end-diastolic diameter over a 1- to 2-min period following pressure elevation (after initial distension), was observed in the majority of rat mesenteric lymphatic vessels in vitro and occurred over a relatively wide pressure range (1-15 cmH2O). Myogenic dilation, a time-dependent rise in end-diastolic diameter following pressure reduction, was observed in over half the vessels equilibrated at a low baseline pressure. Myogenic constrictions were independent of the cardiac-like and time-dependent compensatory decline in end-systolic diameter and increase in amplitude observed in almost all vessels following pressure elevation. Substance P increased the percentage of vessels exhibiting myogenic constriction, the magnitude and rate of constriction, and the pressure range over which constriction occurred. Our results demonstrate that myogenic responses occur in collecting lymphatic vessels and suggest that the response may aid in preventing vessel overdistension during inflammation/edema.
 ...
PMID:Myogenic constriction and dilation of isolated lymphatic vessels. 1902 93


1 2 Next >>