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 occurrence of tachykinins in sensory neurons of the guinea-pig was studied by means of radioimmunoassay combined with ion-exchange and high-performance liquid chromatography as well as by immunohistochemistry. Antisera raised against kassinin (antiserum K12), neurokinin A (NKA) (antiserum NKA2) and substance P (SP) (antisera SP25 and SP2) were used. Antiserum K12 detected NKA, neuropeptide K (NPK) and a component eluting in the position of eledoisin (ELE) in extracts of the lung and ureter. Neurokinin B (NKB) was, however, not found. Neutral water extraction favored recovery of NKA and of the ELE-like component, while NPK was found only in acid extracts. The SP antisera detected two immunoreactive components of which the major form coeluted with synthetic SP. Capsaicin pretreatment depleted all these various forms of immunoreactivity in several peripheral organs including the ureter and lung. The immunoreactivity detected by antisera K12 or SP25 in radioimmunoassay had a similar regional distribution pattern in peripheral tissues. Immunohistochemical examination revealed that antiserum NKA2 stained the same spinal ganglion cells as the SP2 antiserum. The distribution of capsaicin-sensitive nerve fibers stained by these two antisera was also identical in peripheral organs such as the ureter, inferior mesenteric ganglion, heart and lung. It is concluded that multiple tachykinins, including SP, NKA, NPK and an ELE-like peptide, are present in capsaicin-sensitive sensory nerves in the guinea-pig. This finding can most likely be related to the origin of SP, NKA and NPK from the same precursor molecule, subsequent posttranslational tissue processing and axonal transport to terminal regions.
 ...
PMID:Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. 241 71

The innervation of rat and guinea pig urinary tract was examined using immunohistochemistry, radioimmunoassay and True Blue retrograde tracing techniques and was further assessed following both surgical and chemical denervation experiments. Substantial amounts of calcitonin gene-related peptide-like immunoreactivity (range 20-150 pmol/g) were detected in tissue extracts and localised to nerve fibres distributed throughout the urinary tract of both species, these being concentrated in the ureter and base of the bladder. In the guinea pig, the number and distribution pattern of calcitonin gene-related peptide-like immunoreactive nerves appeared to be identical to that of substance P-containing nerves, whereas in the rat the former predominated. Seven days after injection of the fluorescent dye True Blue into tissues of the urinary tract, retrogradely labelled cells were found in the dorsal root ganglia. These cells had a segmental distribution pattern which was specific for each of the injection sites. Thus, after injection of True Blue into the left kidney hilum a single group of labelled cells were found in the ipsilateral T10-L2 dorsal root ganglia. In contrast, injection into the left ureter produced labelled cells in two separate groups of ipsilateral ganglia (T11-L3 and L6-S1). Injection into the wall of the bladder and upper urethra resulted in bilateral labelling, with most labelled cells occurring in L6 and S1 ganglia. Approximately 90% of labelled cells in T10-L3 dorsal root ganglia displayed calcitonin gene-related peptide-like immunoreactivity, but only 60% of retrogradely labelled bladder neurons in L6-S1 ganglia were immunoreactive for this peptide. Adult guinea pigs and neonatal rats injected systemically with capsaicin subsequently exhibited a marked reduction both in the amount of calcitonin gene-related peptide immunostaining and the concentration of immunoreactive material in the urinary tract, dorsal root ganglia and spinal cord. In rats treated neonatally with capsaicin, there was a significant reduction in the number of retrogradely labelled cells and a hypertrophy of the bladder. Sectioning of the pelvic and hypogastric nerves in the rat also resulted in a depletion of calcitonin gene-related peptide-like immunoreactive nerves in the bladder, whereas chemical sympathectomy appeared to have no effect. The results indicate that calcitonin gene-related peptide immunoreactivity occurs in a major proportion of afferent neurons supplying the urinary tract of the rat and guinea pig.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry. 242 72

Antidromic stimulation of sensory nerves or administration of capsaicin and SP in the guinea-pig induced vascular protein leakage with a similar pattern of distribution in different peripheral organs, characterized by a wide-spread but highly selective occurrence. The protein-extravasation responses in the tissues, following nerve stimulation or i.v. capsaicin, were highly correlated with the concentration of SP-LI. Systemic capsaicin treatment caused an almost total loss of SP-LI in visceral organs, in which the extravasation responses to capsaicin or nerve stimulation were also abolished. The ureter of the guinea-pig was most densely innervated by capsaicin-sensitive sensory nerves, which arrive at the rostral part of the ureter via the inferior mesenteric ganglion. The caudal ureter was mainly innervated from the pelvic nerves. The vascular permeability increase induced by SP or capsaicin was more pronounced in the ureter than in any other organ investigated. SP-LI, TK-LI and CGRP-LI coexist in sensory neurons of the guinea-pig and man, as shown by immunohistochemistry. These three kinds of immunoreactivity were found in sensory cell bodies with similar regional and terminal distribution patterns in both the central and peripheral areas. Systemic capsaicin treatment induced marked reduction of SP- and TK-LI in peripheral organs except for the ileum. CGRP-LI in the ureter was also sensitive to the capsaicin treatment. Characterization of the TK-LI (K12) of the guinea-pig ureter and lung, using ion-exchange chromatography and HPLC, demonstrated that at least three immunoreactive components corresponding to NKA, NPK and ELE were present. The major form of SP-LI eluted in the same position as synthetic SP. The NKA- and ELE-like components were also identified by HPLC in water extracts of human ureter. NKB was not detectable in the sensory neurons of the guinea-pig. Capsaicin caused an acute release of SP-, NKA- and ELE-like components from superfused slices of both the spinal cord and ureter of the guinea-pig in vitro. The release of tachykinins by capsaicin was calcium-dependent but tetrodotoxin-resistant. No detectable release of NKB- or NPK-LI was induced by capsaicin. Tachykinins share a common spectrum of biological activities with regard to hypotension, bronchoconstriction and protein extravasation when given systemically to guinea-pigs. The potency of the hypotensive action of tachykinins was similar. NKA and NPK evoked much stronger bronchoconstrictor effects than SP, while SP was more active than NKA in inducing vascular permeability changes.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. 243 Apr 27

The release of tachykinins from isolated slice preparations of the guinea-pig spinal cord and ureter was studied in vitro. Capsaicin (10 microM) caused release of substance P, neurokinin A and an eledoisin-like component from both the spinal cord and ureter. The release of tachykinins induced by capsaicin or potassium (60 mM) was calcium dependent. No detectable release of neurokinin B or neuropeptide K, an N-terminally extended form of neurokinin A, was induced by capsaicin. No detectable release of tachykinins could be demonstrated after exposure to agents which are known to activate C-fibre afferents, such as histamine, bradykinin, serotonin, prostaglandins E1, E2 or acetylcholine. Protein extravasation in the ureter, as determined by the Evans Blue extravasation technique was used as a functional correlate to the tachykinin release. Protein extravasation was induced in vivo by local intraluminal injections of capsaicin at several hundred-fold lower concentrations than those required to induce a detectable release of tachykinins in vitro. The difference may, however, partly depend on the experimental conditions and the detection limit of the tachykinin assay used. The protein extravasation response to capsaicin was absent after systemic capsaicin pretreatment, which causes a marked depletion of tachykinins in the ureter. In conclusion, capsaicin evokes release of several tachykinins from both central and peripheral endings of primary afferent neurons. The peptides released from sensory nerves in the periphery may induce effects such as protein extravasation and smooth muscle contraction.
 ...
PMID:Capsaicin induced release of multiple tachykinins (substance P, neurokinin A and eledoisin-like material) from guinea-pig spinal cord and ureter. 243 50

The effects of capsaicin, in relation to substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) and calcitonin gene-related peptide (CGRP) which coexist in local sensory nerves, on the motility of the guinea-pig ureter were studied in vivo and in vitro. Capsaicin in a low dose (10 nmol kg-1) given i.v. inhibited spontaneous, peristaltic contractions, as revealed by perfusion-pressure changes of the constantly perfused ureter in vivo. This action was independent of autonomic reflexes and prostaglandin formation. Capsaicin stimulated ureteric motility at higher doses (100 and 500 nmol kg-1). The dual effects of capsaicin on the ureteric contractility were absent 2 weeks after systemic capsaicin treatment, which depletes sensory neuropeptides. Both NKA and NPK initiated, as well as increased, the magnitude of the peristaltic contractions of the ureter, while SP only caused a minor excitatory effect. The CGRP inhibited spontaneous, as well as NKA- and NPK-induced ureteric peristaltic contractions. In vitro experiments on the ureter revealed that capsaicin (10(-6) M) induced phasic circular muscle contractions in 60% of the experiments. Neurokinin A, NPK and SP consistently increased the contractile activity. The NKA tachyphylaxis inhibited the contractile response to other tachykinins and capsaicin. The SP analogue Spantide (/D-Arg1, D-Trp7,9, Leu11/-SP) inhibited the contractile responses to SP, NKA and NPK. The CGRP also inhibited the NKA- and NPK-induced contractions of the ureter in vitro. In conclusion, capsaicin, which induces the release of mediators from sensory nerves within the ureter, has either stimulatory or inhibitory effects on ureteric smooth muscle, depending on the in vivo dose administered. The inhibitory response at a low capsaicin dose is similar to the effect of CGRP, while the contractile effects at higher doses resemble the response to tachykinins.
 ...
PMID:Dual capsaicin effects on ureteric motility: low dose inhibition mediated by calcitonin gene-related peptide and high dose stimulation by tachykinins? 243 98

The presence of calcitonin-gene related peptide (CGRP)-like immunoreactivity (-LI) in sensory neurons was established by immunohistochemistry and radioimmunoassay (RIA) in combination with high performance liquid chromatography (HPLC). CGRP-immunoreactive (-IR) nerve fibres were present in many peripheral organs including heart, ureter, uterus and gall bladder of guinea-pig and man. The distribution of CGRP-IR nerves in the dorsal horn of the spinal cord, of positive cell bodies in thoracic spinal and nodose ganglia and nerves in peripheral organs was closely related to that of substance P-LI. Double staining experiments revealed that in most cases peripheral CGRP-IR nerve terminals also contained SP-LI. However, different localization of SP- and CGRP-IR neurons was observed in the nucleus of the solitary tract as well as in the ventral horn of the spinal cord. In the heart, CGRP-IR nerves were associated with myocardial cells (mainly atria), coronary vessels, local parasympathetic ganglia as well as with the epi- and endocardia. Three to 4-fold higher levels of native CGRP-LI were observed in the atria than in the ventricles of the heart. HPLC analysis revealed that the major peak of CGRP-LI in the heart of rat and man had the same retention times as the synthetic equivalents. Systemic capsaicin pretreatment and adult guinea-pigs caused a loss of CGRP-IR terminals in the dorsal horn of the spinal cord as well as in peripheral organs including the heart. After capsaicin treatment, the content of CGRP-IR was reduced by 70% in the heart and by 60% in the dorsal part of the spinal cord. In superfusion experiments with slices from the rat spinal cord, a release of CGRP-LI was induced by 60 mM K+ and 3 microM capsaicin in a calcium-dependent manner.
 ...
PMID:Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. 243 68

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. The capsaicin-(1 microM) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4 degrees C). Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides.
 ...
PMID:Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract. 244 29

The effects of neurokinins (NKs), tachykinins and some NK-related peptides (selective agonists for the NK-1, NK-2 or NK-3 receptors) have been investigated in the various sections of the rat lower urinary tract. In the isolated bladder, all peptides were substantially equipotent with the exception of senktide, an NK-3 agonist, which was distinctly less potent than the other compounds. Similar results were obtained in the isolated urethra. In these tissues, the maximal response to NK-1 agonists was distinctly less intense than that to the other peptides. In the bladder, exposure to phenoxybenzamine (30 microM for 90 min) reduced the response to NK-A but not that to substance P, KCl or field stimulation. In the isolated ureter, peptides active at both the NK-2 and the NK-3 sites [including senktide and [MePhe7]-NKB(4-10)] activated, at nanomolar concentrations a series of rhythmic contractions, whereas peptides active at the NK-1 site, were active only at micromolar concentrations. These findings provide further evidence that multiple NK receptors are present in the rat lower urinary tract. In the bladder, NK-2 and NK-1 sites mediate the direct response to NKs, in accordance with binding and autoradiographic data. In the ureter, both NK-2 and NK-3 sites may activate the direct contractile response to these substances.
 ...
PMID:Neurokinin receptors in the rat lower urinary tract. 245 93

1. Intracellular recordings were made from neurones of the guinea-pig inferior mesenteric ganglion (IMG) maintained in vitro with both ureters and major nerve trunks attached. Afferent fibres in the ureteric nerve were activated by electrical, chemical and mechanical stimuli. 2. Repetitive stimulation of a ureteric nerve branch evoked a non-cholinergic, synaptic slow excitatory potential (slow EPSP) in 48% of neurons. The amplitude of the slow EPSP was dependent on membrane potential and was decreased by membrane depolarization and increased by hyperpolarization. 3. The slow EPSP was attenuated or abolished by capsaicin (1 microM), which itself depolarized IMG neurones. Substance P (2 microM) or neurokinin A (2 microM) also depolarized IMG neurones and in the presence of these tachykinins the slow EPSP was attenuated or abolished. 4. Distension of the ureter evoked a non-cholinergic slow depolarization in 45% of IMG neurones which was abolished by tetrodotoxin (1 microM) and by capsaicin (1 microM). 5. Chemical stimulation of ureteric afferent nerve terminals by intralumenal perfusions of the ureter with capsaicin (1 microM) produced a slow depolarization in the IMG which was prevented by blocking nerve conduction with TTX. 6. These data demonstrate that electrical stimulation of ureteric afferent fibres produces a non-cholinergic slow EPSP in the IMG. Primary afferent (capsaicin-sensitive) C fibres are also activated by distension of the ureter and evoke a slow depolarization in the IMG. The synaptic mediator of these events is likely to be tachykinin(s) released from capsaicin-sensitive C fibres. These fibres may be mechanosensory and/or nociceptive.
 ...
PMID:Stimulation of afferent fibres of the guinea-pig ureter evokes potentials in inferior mesenteric ganglion neurones. 246 85

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) has been measured in various tissues of control rats and rats pretreated with systemic capsaicin, s.c. (50 mg/kg as newborns or as adults, 125 mg/kg as adults) and compared with the tissue level of substance P- and tachykinin-like immunoreactivities (SP-LI and TK-LI). The rank order of CGRP-LI concentration in various tissues was as follows: trigeminal ganglion greater than urinary bladder greater than ureter much greater than distal duodenum much greater than proximal duodenum much greater than skin (snout) greater than thymus = right atrium = vas deferens. A complete depletion of CGRP-LI following capsaicin treatment of both adult and newborn animals was observed in urinary bladder, ureter, atrium, vas deferens and skin. Capsaicin pretreatment of both adult and newborn rats reduced CGRP-LI in the duodenum by about 50%. CGRP-LI in trigeminal ganglion was reduced only in newborn animals, while it was not affected in the thymus. The CGRP-LI/SO-LI ratio varied in these tissues between 33.2 (urinary bladder) and 0.9 (proximal duodenum). A significant correlation was found between CGRP-LI and SP-LI or TK-LI in tissues where immunoreactivities were depleted by capsaicin, as well as in the urinary bladder of individual animals. The correlation between CGRP-LI with SP-LI and TK-LI upon treatment with capsaicin indicates that neurons containing SP and TK as well as CGRP, and neurons containing CGRP only, are affected in a similar manner by capsaicin.
 ...
PMID:Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: correlation with substance P and other tachykinins and sensitivity to capsaicin. 246 30


<< Previous 1 2 3 4 5 6 Next >>