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 and a series of related neurokinins having various degrees of selectivity for tachykinin receptors have been studied for their effects on gastric acid secretion both "in vitro" and "in vivo". In the isolated gastric fundus from immature rats, substance P, the C-terminal heptapeptide of neurokinin A, NKA (4-10), [Arg]NKB and two synthetic analogues of NKA (4-10), namely, [beta-Ala8]NKA (4-10) and [Ala5]NKA (4-10) (compounds marked Men 10210 and Men 10209, respectively) had no effect on spontaneous secretion but enhanced the secretory response to histamine. All the different neurokinins were effective in the range of concentrations 10(-7) - 10(-6) M. In the conscious cat with gastric fistula, substance P dose-dependently increased basal acid secretion, whereas Men 10210 was absolutely ineffective. Men 10209 caused a slight increase in acid output which, however, was only 10% of that induced by dimaprit or pentagastrin. The secretory effect of dimaprit and pentagastrin was not affected by the different neurokinins, conversely the response to 2-Deoxy-D-glucose was slightly reduced by Men 10210 (10 nmol/kg/h). The above data suggest that the natural and synthetic neurokinins studied have negligible effects on gastric acid secretion, thus the gastro-protective effect observed in some experimental conditions is unlikely to be related to an antisecretory effect of these compounds.
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PMID:Effect of substance P and related neurokinins on gastric acid secretion. 171 76

Tachykinins and CGRP label two distinct populations of neurons innervating the digestive system: intrinsic and extrinsic, afferents. The bulk of SP/tachykinin innervation originates from intrinsic neurons, even though a minor component of this innervation derives from afferent neurons, which are mostly located in dorsal root ganglia. Afferent SP/tachykinin fibers are mainly confined to a perivascular location and to the submocosa in the gut, but are distributed also to the hepatobiliary pathway and pancreas. On the contrary, the extrinsic CGRP-containing afferents form a major component of the sensory innervation of the alimentary tract, including the rich CGRP innervation of the esophagus, stomach, hepatobiliary tract, pancreas, and vasculature, as well as a portion of non-vascular fibers distributed to the intestinal wall. Tachykinin and CGRP immunoreactivities appear to be colocalized in a population of nerve fibers, which are likely to be extrinsic, afferent, since colocalization of these peptide immunoreactivities has not been reported in intrinsic neurons. The presence of SP/NKA-encoding transcripts in the enteric nervous system and sensory ganglia and the lack of hybridization signal with RNA probes complementary to NKB mRNA indicate that the PPT I gene, but not the PPT II gene, is transcribed in these structures. This observation, along with receptor binding sites and radioimmunoassay data, which have failed to detect NKB receptor binding sites or immunoreactivity (Eysselein et al., 1990; Maggio, 1988; Mantyh et al., 1988; 1989) in the intestine of several mammals, is consistent with a differential expression of the two PPT genes in the periphery and in the central nervous system (Brecha et al., 1989; Warden and Young, 1988). A differential expression of the tachykinin-encoding genes, the existence of multiple tachykinin receptor subtypes (Mantyh et al., 1988; 1989), and the findings that tachykinins can be differentiated on the basis of the potency of their activities (Galligan et al., 1987; Maggio, 1988), support the possibility that each tachykinin is expressed in separate, and perhaps functionally distinct neuronal systems. alpha- and beta-CGRP genes also are differentially expressed according to the neuronal populations: alpha-CGRP mRNA is the most prominent form in sensory ganglia, and beta-CGRP mRNA is the only form detected in enteric neurons (Mulderry et al., 1988; Sternini and Anderson, 1990). In addition, distinct distributions of mRNAs generated from the two CGRP genes have been reported in the central nervous system (Amara et al., 1985). The differential expression patterns of alpha- and beta-CGRP mRNAs are consistent with a differential regulation of the alpha- and beta-CGRP genes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tachykinin and calcitonin gene-related peptide immunoreactivities and mRNAs in the mammalian enteric nervous system and sensory ganglia. 195 Jul 91

The tracheobronchial vasculature is controlled by adrenergic, cholinergic, and peptidergic nervous mechanisms. Sympathetic nerves release norepinephrine and neuropeptide Y (NPY), which are both constrictor agents, the latter being long-lasting. Parasympathetic nerves release acetylcholine and usually vasoactive intestinal polypeptide (VIP), both of which are vasodilators, VIP being the longer lasting. These motor nerves are controlled by many reflex inputs. Activation of pulmonary C-fiber receptors by irritants and inflammatory mediators causes a powerful vasodilatation, mainly via sympathetic motor nerves. Cardiac and chemoreceptor reflexes also influence airway vascular tone. Sensory nerves in the airway mucosa are responsible for local axon reflexes in response to irritants and inflammatory mediators. These nerves contain neuropeptides such as substance P (SP), neurokinins A and B (NKA, NKB), and calcitonin gene-related peptide (CGRP). All these neuropeptides are powerful vasodilators. Thus, inflammatory conditions in the lungs such as asthma cause vasodilation by local direct action of mediators, by axon reflexes, and by central nervous reflexes. The vasodilation could lead to mucosal edema. Thus, airway vascular responses have to be added to bronchoconstriction and mucus secretion as part of the mucosal pathology of asthma.
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PMID:Neural control of airway vasculature and edema. 200 85

The contractile response to natural tachykinins [substance P (SP), neurokinin A (NKA), arginin-neurokinin B (ArgNKB)] and to synthetic peptide [Pro9]SP sulfone, [beta Ala8]NKA(4-10) and [MePhe7]NKB, were investigated in the isolated smooth muscle from the human prostatic urethra. Natural tachykinins evoked concentration-related responses with the following order of potency: NKA----NKB--------SP. Among selective agonists [beta Ala8]NKA(4-10) produced concentration-related contractions, while [Pro9]SP sulfone and [MePhe7]NKB were inactive. These data indicate the presence of NK-2 receptors in the smooth muscle of the human prostatic urethra.
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PMID:The contractile effect of tachykinins on human prostatic urethra: involvement of NK-2 receptors. 217 70

The different structures of the nasal, tracheal and bronchial vascular beds are described. All the vasculatures are influenced by neuropeptides released from three types of nerve: (1) sympathetic nerves release both noradrenaline and neuropeptide Y (NPY), both of which cause vasoconstriction; (2) parasympathetic nerves release both acetylcholine and either vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) or peptide histidine isoleucine (PHI), all of which cause vasodilatation; and (3) sensory nerves release sensory neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinins A and B (NKA, NKB). Direct application of the neuropeptides to various preparations of the vascular beds confirms their actions. Stimulation of nerves to the airways in vivo causes vascular changes in the presence of anti-acetylcholine, anti-noradrenaline and ganglionic-blocking drugs, suggesting that they are mediated by neuropeptides. Reflex activation of the parasympathetic and sympathetic nerves to the airway vasculature has been established, but the relative importance of classical neurotransmitters and of neuropeptides has not been analyzed. The neuropeptides in sensory nerves are released when the nerves are stimulated by capsaicin, various chemical irritants and inflammatory mediators such as histamine and bradykinin. The sensory neuropeptides cause not only vasodilatation but also, in some instances, extravasation of plasma protein and an increase in interstitial fluid volume. The interaction of the different neuropeptide systems, and their interplay with classical transmitters released from motor nerves, require further exploration.
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PMID:The NANC system and airway vasculature. 219 62

Antiserum was raised against kassinin in rabbits. Cross-reactivity with other tachykinins was determined; these included substance K (100%) and substance P (0.1%). Peptides extracted from rat brain and synthetic tachykinins were chromatographed by reverse-phase HPLC. The major peak of kassinin-like material eluted at a time different from that of synthetic kassinin, eledoisin, physalaemin, neurokinin beta, and substance P but coeluted with substance K. Measurement of kassinin-like material in macrodissected and microdissected brain regions indicated that the distribution of kassinin-like material was similar to that of substance P.
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PMID:Demonstration and distribution of kassinin-like material (substance K) in the rat central nervous system. 240 32

Recently, two kassinin-like tachykinins have been isolated from mammalian nervous tissue. The potencies of these peptides, substance K (neurokinin alpha) and neuromedin K (neurokinin beta) were compared with those of substance P, eledoisin, and kassinin in various pharmacological systems in vivo and in vitro. In contracting the isolated guinea-pig ileum and rabbit jejunum the potencies of eledoisin, kassinin, substance K, and neuromedin K were 13-80% that of substance P. In the rat vas deferens substance K and neuromedin K potentiated the electrically induced contractions with potencies similar to those of eledoisin and kassinin; they were 46-236 times as potent as substance P. In stimulating salivation in the rat after intravenous injection, eledoisin, kassinin, and substance K were respectively 2.3, 1.3 and 0.33 times as potent as substance P. In contrast, neuromedin K exhibited negligible activity. Each peptide tested led to a short fall in blood pressure after intravenous injection in the rabbit, substance P being 12-250 times as potent as the other peptides. Substance P was 20 times as potent as substance K or neuromedin K in inducing vasodilatation in the rat hind paw in vivo. Of the peptides tested, only substance P (10 nmol/min) significantly increased the release of histamine from the rat isolated hindquarter preparation. The results are discussed with respect to several theories of tachykinin receptor heterogeneity.
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PMID:In vivo and in vitro actions of mammalian tachykinins. 241 73

The regional distribution of 3 mammalian tachykinins (substance P, neurokinin alpha and neurokinin beta) in the rat spinal cord and related structures was investigated using a method of radioimmunoassay combined with high performance liquid chromatography. Substance P and neurokinin alpha were found to be distributed in a very similar manner with fairly constant molar ratios i.e. ratios of substance P to neurokinin alpha were 3.69 in the dorsal root ganglia, 3.49 in the dorsal root and 3.09 in the dorsal horn of the cervical spinal cord. On the other hand, the distribution of neurokinin beta was different from other tachykinins; although concentrated in the dorsal horn, neurokinin beta in the dorsal root ganglia or in the dorsal roots was negligibly small in amount. When the cervical dorsal roots were sectioned unilaterally, substance P and neurokinin alpha were decreased in a parallel fashion in the dorsal horn, whereas neurokinin beta was not. In addition neurokinin alpha was selectively and significantly decreased in the dorsal horn of the intact side when compared to that in the unoperated control rat. Since the magnitude of a decrease of neurokinin alpha in molar basis was approximately the same as a decrease of substance P, these findings suggest that the neurokinin alpha and substance P-containing primary afferent fibres could project partly to the contralateral dorsal horn as well. When the thoracic spinal cord was transected, substance P (and neurokinin alpha) was decreased in the ventral part of the lumbar spinal cord, suggesting the presence of tachykinin(s)-containing descending fibres.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional distribution of substance P, neurokinin alpha and neurokinin beta in rat spinal cord, nerve roots and dorsal root ganglia, and the effects of dorsal root section or spinal transection. 241 94

Antisera were raised in rabbits against the tachykinins neurokinin A (NKA) and substance P (SP). All NKA-antisera tested cross-reacted markedly with NKB, kassinin and eledoisin in radioimmunoassay (RIA), but virtually not with SP and physalaemin. Also when used for immunohistochemistry, one of the NKA-antisera was found to be virtually without cross-reactivity with SP. The most specific SP-antiserum did not cross-react with NKA but to some extent with NKB at the immunohistochemical level. Using these two antisera, the same distribution pattern of immunoreactivity was seen in both the rat substantia nigra and dorsal spinal cord. In neutral extracts of the substantia nigra, all NKA-antisera used for RIA detected a major component which eluted at the position of NKA in reverse phase high performance liquid chromatography, while no or only little immunoreactivity was detected at the position of NKB. A major component of substance P-like immunoreactivity (SPLI) co-eluting with SP and one or two minor SPLI-components were also detected in these extracts. An SP-antiserum, which cross-reacted markedly with physalaemin, detected an additional rather prominent component. In neutral water extracts of dorsal spinal cord the component detected with the NKA-antisera at the position of NKB, as well as one of the SPLI-components not eluting in the position of SP, were much more prominent than in the corresponding extracts of substantia nigra. In acetic acid extracts of both tissues, only one major SPLI-component co-eluting with SP could be detected, while only very small amounts of immunoreactivity eluting at the position of NKA and NKB (dorsal spinal cord only) could be detected using the NKA-antisera. The present results illustrate the importance of the extraction method used in immunochemical studies and demonstrate that the relative proportions of various tachykinins are markedly different in the rat substantia nigra and dorsal spinal cord.
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PMID:Tachykinin multiplicity in rat central nervous system as studied using antisera raised against substance P and neurokinin A. 242 6

The plasma concentrations of various tachykinins were measured before and during flushing episodes in 16 patients with metastatic carcinoid tumors. The flushing attacks were induced by iv injection of pentagastrin or ingestion of food or alcohol. Tachykinins, such as neurokinin A (NKA) and neuropeptide K (NPK), increased 2-fold during flushing episodes in 12 patients, and the plasma concentrations of substance P increased to a varying extent in 3 patients. Chromatographic analysis of plasma samples taken before and during flushing episodes in 2 patients indicated the presence of individual spectra of tachykinins. In addition, the plasma concentration of tachykinin [TKLI(K12)], using an assay that detects NKA, NPK, kassinin, eledoisin, and NKB, but not substance P and physalaemin, and the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA) were measured in 20 patients with midgut carcinoid tumors before and during treatment with human leucocyte interferon. The overall changes in the 2 tumor markers were concordant in 18 of the 20 patients. Thus, the Spearman correlation coefficient between the percent changes in urinary 5-hydroxyindole acid excretion and plasma TKLI(K12) was 0.54 (P less than 0.001). The patients who had a decrease in the tumor markers also had a decrease in flushing episodes and diarrhea. Plasma TKLI(K12) is a convenient tumor marker for the diagnosis and follow-up of patients with carcinoid tumors of midgut origin. The combined use of both tumor markers strengthens the diagnosis and may improve the evaluation of response during treatment.
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PMID:Tachykinins in carcinoid tumors: their use as a tumor marker and possible role in the carcinoid flush. 242 99


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