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)

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
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PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72

Antisera raised against neuron specific enolase (NSE), substance P, vasoactive intestinal peptide (VIP) and tyrosine hydroxylase (TH) were used to reveal nerve fibres in the wall of the canine small and large intestine. The circular muscle of the colon was innervated by nerve fibre bundles that ran parallel to the muscle throughout its thickness. A plexus of fibre bundles was found against the inner (submucosal) surface of the circular muscle. Fibres with substance P, VIP and TH immunoreactivity all contributed to this innervation. The circular muscle of the small intestine was distinctly separated into outer and inner layers by a dense plexus of nerve fibres, the deep muscular plexus. The outer and inner circular muscle were innervated by substance P, VIP and TH fibres. Extrinsic denervation through the severing of nerve fibres in the mesentery caused TH fibres in the intestine to degenerate, but had no detectable effect on the fibres with substance P or VIP immunoreactivity. Myectomy (the removal of the myenteric plexus from the full circumference of the intestine over a distance of 2-3 cm), performed 7-13 days before tissue was taken, resulted in an almost complete loss of substance P fibres from the circular muscle of the colon and the outer circular muscle of the small intestine. However, many fibres persisted in the deep muscular plexus of the small intestine, and most fibres remained in its inner circular muscle. The changes in distribution of VIP fibres were almost identical, except that a small proportion of reactive fibres remained in the circular muscle of the colon and the outer circular muscle of the small intestine. It is concluded that the circular muscle layers of the small intestine and colon have dual sources of intrinsic nerve supply: the myenteric ganglia supply fibres primarily to the outer part of the muscle and the submucous ganglia supply fibres to the inner muscle. The present study further demonstrated that VIP fibres ran anally in the myenteric plexus of both the small and large intestine, whereas substance P fibres ran orally in the large intestine and both orally and anally in the small intestine. The innervation of the muscularis mucosae and mucosa by substance P and VIP fibres was not affected by myectomy or extrinsic denervation, and these structures are therefore likely to be innervated by nerve cells in the submucous ganglia.
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PMID:Projections of substance P, vasoactive intestinal peptide and tyrosine hydroxylase immunoreactive nerve fibres in the canine intestine, with special reference to the innervation of the circular muscle. 169 12

The distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle.
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PMID:Neuropeptide-containing nerve fibers in the pharynx of the rabbit. 169 87

Using immunocytochemistry, the authors studied the peptidergic innervation to the vasculature of the optic nerve and retina in the rhesus monkey and rat. In the monkey, beaded nerve fibers immunoreactive to the vasoactive peptides, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal peptide (VIP), are present in the adventitia and perivascular space along the course of the central retinal artery within the optic nerve. The CGRP and SP immunoreactivities fully co-localize. Perivascular peptidergic nerve fibers terminate as the blood vessel enters the globe and do not follow the branches of the central retinal artery inside the eye. Within the substance of the optic nerve behind the lamina cribrosa, small blood vessels occasionally are supplied with CGRP-, SP-, and sometimes NPY- or VIP-immunoreactive nerve fibers. Of special note, fine nerve fibers not clearly related to blood vessels are seen within the lamina cribrosa; their simultaneous immunoreactivity to CGRP and SP suggests a sensory function. In the rat as in the monkey, the retinal arterioles beyond the surface of the optic disc lack evident peptidergic innervation. Perhaps an explanation for the known physiologic reactivity of the retinal circulation to neurohumors in the absence of recognizable peripheral innervation can be based on comparison to the brain where intraparenchymal blood vessels may be regulated by local neurons. Since the inner plexiform layer has abundant amacrine-derived nerve processes containing classical neurotransmitters and/or neuropeptides, a local mechanism coupled to intrinsic retinal activity might contribute to the regulation of the circulation.
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PMID:Peptidergic innervation of the retinal vasculature and optic nerve head. 169 44

We investigated the effect of octreotide (OCT), a stable somatostatin analog, (OCT) on changes in short-circuit current (Isc) induced by vasoactive intestinal peptide (VIP), aminophylline, serotonin (5-HT) and substance P. OCT significantly decreased basal Isc at a concentration of 10(-9) M; the maximum decrease in Isc was observed at 10(-6) M. OCT (10(-7) M) significantly inhibited the intestinal secretory response to all the secretagogues studied. The maximum Isc response was reduced when tissues were stimulated with VIP (184.9 +/- 18.0 vs. 119.7 +/- 14.1, P less than 0.05), 5-HT (135.1 +/- 14.4 vs. 79.5 +/- 13.4, P less than 0.05) and substance P (156.0 +/- 19.2 vs. 30.7 +/- 5.4, P less than 0.01). In the case of aminophylline, the concentration-response curve was shifted to the right but the maximum response was not reduced. Because VIP and aminophylline increase cAMP while 5-HT and substance P stimulate intestinal secretion principally by a calcium linked mechanism, we conclude that OCT inhibits Isc in rat colon by more than one mechanism.
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PMID:Octreotide inhibits increases in short-circuit current induced in rat colon by VIP, substance P, serotonin and aminophylline. 169 51

Substance P produced a dose-dependent, long-lasting hyperpolarization of the membrane of the Schwann cells of the giant nerve fibre of the tropical squid. A survey of the effectiveness of a range of other naturally occurring tachykinin agonists suggested that the receptors present on the squid Schwann cell belong to the subtype SP-P or NK1, for which substance P is the preferred agonist. A survey of the effectiveness of a range of substance P fragments indicated that the direct hyperpolarizing effects of the substance P molecule were mediated by peptides with an intact amidated C-terminal. However, a second subset of receptors that can be activated by N-terminal fragments and analogues lacking an amidated C-terminal was also present in this preparation. The non-subtype-specific antagonist D-Arg1,D-Trp7,9,Leu11 substance P (spantide) was a potent blocker of the effects of substance P in this preparation. Activation of the substance P receptors did not interact with the effects induced by activation of either the nicotinic cholinergic receptors or octopaminergic receptors present in this preparation. However, it did potentiate the effects of activation of the receptors for vasoactive intestinal peptide (VIP), either in response to bath application of the peptide or due to their activation by the release of an endogenous VIP-like peptide after stimulation of the giant axon.
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PMID:Substance P modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre. 169 92

Gastrin-releasing peptide (GRP) and bombesin can stimulate pepsinogen release by both gastrin-dependent and -independent mechanisms. Using isolated guinea pig gastric chief cells, we determined that GRP can act directly on the guinea pig chief cell to cause pepsinogen release. GRP and bombesin stimulated a 2.5- to 3-fold increase in pepsinogen release above basal release. Substance P also stimulated a small but significant increase in pepsinogen release. No gastrin immunoreactivity was detected in the supernatants of cells stimulated with up to 1 microM GRP or bombesin or 1 mM carbachol. GRP-stimulated pepsinogen release was completely inhibited by GRP/bombesin receptor agonists as well as substance P receptor antagonist but not by antagonists to receptors for gastrin, the octapeptide of cholecystokinin (CCK-8), secretin, vasoactive intestinal peptide (VIP), or muscarinic agents. Substance P-stimulated pepsinogen release was completely inhibited by substance P receptor antagonist but not by GRP/bombesin receptor antagonists. An additive effect on pepsinogen release was seen when GRP was combined with maximally effective concentrations of adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (VIP, secretin, 8-BrcAMP) but not with calcium-mediated agents (carbachol, CCK-8, gastrin). These results indicate that GRP can directly stimulate pepsinogen release from guinea pig chief cells by a specific GRP receptor that mobilizes intracellular calcium.
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PMID:Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells. 170 Jun 25

The effects of the tachykinin antagonist Spantide II (D-Nic-Lys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nl e11)-substance P (SP) and the vasoactive intestinal peptide (VIP) antagonist (Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 on the excitability of the spinal nociceptive flexor reflex to intrathecally (i.t.) applied SP and VIP, respectively, as well as the facilitation evoked by activation of cutaneous C-afferent was examined. Both antagonists blocked the effects of the respective neuropeptides in rats with both intact and sectioned sciatic nerves. Spantide II antagonised C-afferent induced reflex facilitation in rats with intact nerves, but the degree of antagonism declined after axotomy. In contrast, the VIP antagonist did not block C-afferent induced facilitation in rats with intact nerves, but did so after axotomy. The results indicate that the role of tachykinins in mediating C-afferent-induced reflex facilitation is taken over by VIP after axotomy.
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PMID:Plasticity of the peptidergic mediation of spinal reflex facilitation after peripheral nerve section in the rat. 170 Aug 43

Both carotid bodies from 26 patients coming to necropsy were fixed in 10% neutral buffered formalin and sections 4 microns thick were stained for various peptides by use of the immunogold technique. The results show that the human carotid body contains met- and leu-enkephalin, substance P, vasoactive intestinal peptide (VIP), neurotensin and bombesin. The distribution of these six peptides within the carotid body differs. Thus met- and leu-enkephalin are both present predominantly within glomic chief cells but with a marked tendency to favour the dark variant of these cells. Substance P and VIP both show a weak immunoreactivity in comparison to the enkephalins and are present in all three variants of chief cell. Neurotensin shows the weakest immunoreactivity of all and is restricted to a few glomic chief cells in a minority of cases. Bombesin also shows a weak immunoreactivity in glomic chief cells but a strong reaction in glomic arteries and arterioles. In these vessels bombesin appears to be confined to smooth muscle cells in the media but we cannot say whether it is secreted by them or merely bound to receptor sites on their membranes. These findings are related to quantitative data on the concentration of peptides in the human carotid body from a previous paper with which we were associated.
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PMID:The occurrence and distribution of certain polypeptides within the human carotid body. 170 Sep 31

The effect of intrathecally (i.t.) applied tachykinin antagonist D-NicLys1, 3-Pal3, D-Cl2Phe5, Asn6, D-Trp7.9, Nle11-substance P (SP), spantide II, on the nociceptive flexor reflex was studied in decerebrate, spinalized, unanaesthetized rats over the dose range of 10 ng-10 micrograms. I.t. spantide II usually caused weak facilitation of the flexor reflex, especially at lower doses (10-100 ng) and at higher doses (1-10 micrograms) it sometimes depressed the reflex. Pre-treatment with spantide II (1, 3 or 10 micrograms) effectively antagonized the facilitatory effect of 10 ng i.t. SP on the flexor reflex for about 30 min. The facilitation of the reflex induced by i.t. administration of other neuropeptides present in primary afferents, somatostatin (SOM), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and galanin (GAL), was not influenced by spantide II. This non-toxic antagonist also effectively blocked facilitation of the flexor reflex induced by C-fiber conditioning stimulation of the sural nerve. The present results indicate that spantide II is an effective and specific tachykinin antagonist in the spinal cord. Furthermore, C-fiber stimulation facilitates the nociceptive flexor reflex through a mechanism involving the release of SP from the central terminals of primary afferents.
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PMID:The specific antagonistic effect of intrathecal spantide II on substance P- and C-fiber conditioning stimulation-induced facilitation of the nociceptive flexor reflex in rat. 170 83


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