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)

This paper reports a quantitative in vivo study on the vagal activation of the intramural non-adrenergic, non-cholinergic inhibitory nerves in the ferret gastric corpus. The nature of the inhibitory neurotransmitter was also investigated. In the atropinized, guanethidine-treated, urethane-anaesthetized ferret, electrical stimulation (10 s at 20 V, 1-20 Hz, 0.5 ms pulses) of the cervical vagi produced a prompt fall in intracorpus pressure that was related to the stimulus frequency. The maximal response was achieved at 10 Hz. The time taken for the intracorpus pressure to return to pre-stimulus levels after a 10 s period of stimulation was related to the stimulus frequency; at 10 Hz the pressure took approximately 11 min to recover. In contrast to studies in the cat (Martinson & Muren, 1963), there was no detectable difference in the electrical threshold for activation of the vagal excitatory and vagal inhibitory fibres. The nature of the vagal non-adrenergic, non-cholinergic inhibitory neurotransmitter was investigated using a variety of antagonists and agonists. Adenosine triphosphate (ATP), adenosine, alpha beta-methylene ATP and beta gamma-methylene ATP all contracted the corpus in the presence of vagotomy, atropine, guanethidine and indomethacin. The vagally induced fall in corpus pressure was not blocked by high doses of alpha beta-methylene ATP. A variety of peptides were investigated for their effects on corpus pressure in the presence of atropine, guanethidine and vagotomy. Bombesin, pentagastrin, substance P, cholecystokinin octapeptide (CCK-8) and bradykinin all produced an increase in intracorpus pressure. Neurotensin and vasoactive intestinal polypeptide (VIP) both decreased intracorpus pressure, and of the two VIP most closely mimicked the response to vagal activation of the non-cholinergic, non-adrenergic inhibitory neurones. The results provide support for the involvement of a peptide (possibly VIP) rather than a purine in the vagally driven decrease in intracorpus pressure in the ferret.
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PMID:Characteristics of the vagally driven non-adrenergic, non-cholinergic inhibitory innervation of ferret gastric corpus. 402 Jun 96

Substance P (6.25-25 p-mole) produced dose-dependent flare and wheal responses when injected intradermally into the volar surface of the human forearm. The maximum flare response was obtained within the first 3 min of injection and declined thereafter. The wheal response reached a maximum after 12 min following the injection. Only those peptides having one or more basic residues in the N-terminal region were effective in producing a flare reaction. Eledoisin-related peptide and SP1-9 were 17 and 7 times less active than substance P respectively, whilst [D-pro2, D-phe7, D-trp9]SP1-11 was twice as active. The N-terminal tetrapeptide, SP1-4 and eledoisin were inactive in the dose range tested. Wheal-producing activity was not dependent on the presence of basic residues and the rank order of relative potencies was: physalaemin (2.0): [D-pro2, D-phe7, D-trp9]SP1-11 (1.1): SP1-11 (1.0): SP4-11 (0.4): SP1-9 (0.15): eledoisin-related peptide (0.08): eledoisin (0.06). The N-terminal tetrapeptide failed to produce a wheal response in the dose range tested. Substance P was approximately equi-active with poly-L-arginine in the production of wheal and flare and both of these agents were about 10 times more potent than histamine. Adenosine triphosphate (25-400 n-mole) produced dose-dependent wheal and flare responses and was 10,000 times less potent than substance P. Pre-treatment of the subjects with the H1 histamine antagonist, chlorpheniramine, (20 mg I.V.) reduced the wheal and flare responses to substance P. Local anaesthetic injection into the skin reduced the spread of the flare response but did not affect the development of the wheal response. Pre-treatment of the skin with capsaicin reduced the flare but not the wheal response to intradermal injection of histamine. The results are discussed in relation to the mechanism of the 'axon reflex' vasodilatation in skin. This is thought to involve mast cells in addition to substance P-containing primary afferent neurones.
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PMID:Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. 619 37

The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha-chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin-substance P- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Of the three peptides present, only VIP produced a concentration-dependent relaxation. A substance with VIP-like immunoreactivity was released during nerve-induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium-depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.
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PMID:Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa. 619 89

The stainless steel cannula method was applied to isolated and perfused canine basilar arteries to examine the role of endothelium in the responses to intraluminal vasoactive substances. After intraluminal treatment with saponin to remove the endothelium, the monophasic constrictions to potassium chloride and prostaglandin F2 alpha were potentiated, while those to phenylephrine (alpha 1-adrenoceptor agonist) and 5-hydroxytryptamine were not changed. Xylazine (alpha 2-adrenoceptor agonist) and acetylcholine induced a constriction preceded by a small dilation in controls. The response to xylazine was not modified, while the constriction to acetylcholine was augmented after endothelium removal. Bradykinin, substance P and vasopressin caused a dilation in lower doses, and a dilation followed by a secondary constriction in higher doses in controls. The dilations to these peptides were reduced and the constrictions were enhanced after endothelial removal. Adenosine triphosphate produced a biphasic response, i.e., a dilation followed by a constriction, which was occasionally preceded by a small constriction in higher doses, and only the dilation in lower doses was attenuated. The monophasic dilation to adenosine was potentiated, while the papaverine-induced dilation was not influenced by endothelial removal. After extraluminal treatment with oxyhemoglobin, the dilations to calcium ionophore A23187 and thimerosal were attenuated, while the constriction to acetylcholine was enhanced. The dilations to substance P and vasopressin were depressed, and the constrictions were potentiated. The monophasic dilation to sodium nitroprusside was augmented, while that to papaverine was not changed. These results suggest that the endothelium may play important roles not only in producing endothelium-derived relaxing factors but also in modulating the calcium influx into the smooth muscle cells. The mechanisms of altered responsiveness might be implicated in cerebral vasospasm following subarachnoid hemorrhage.
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PMID:Effects of endothelium removal by saponin and of oxyhemoglobin on canine cerebrovascular responses. 783 71

We conducted this study to analyze endothelial cell function within intact thoracic aorta of the systemic sclerosis murine model, the heterozygous tight-skin mice 1: (i) assessing the distribution and activation intensity of endothelial cells, responsive to endothelium-dependent vasodilators (acetylcholine, adenosine triphosphate, bradykinin, and substance P) and Iloprost, using laser line confocal microscopy in combination with two Ca2+ fluorescent dyes; (ii) evaluating en-dothelium-dependent vasodilator- and Iloprostinduced relaxation, using isometric tension measurement; and (iii) investigating the role of nitric oxide in mediating relaxation to acetylcholine and adenosine triphosphate. The number of activated endothelial cells was significantly lower in heterozygous tight-skin mice 1, compared with controls, for adenosine triphosphate and Iloprost. Maximal increase of Ca2+ fluorescence intensity ratio in activated endothelial cells was decreased for adenosine triphosphate, bradykinin, and Iloprost, in heterozygous tight-skin mice 1. Adenosine triphosphate- and Iloprost-mediated aortic relaxation was further impaired in heterozygous tight-skin mice 1. Finally, aortic relaxation to acetylcholine and adenosine triphosphate was markedly decreased by nitric oxide synthase inhibitor in heterozygous tight-skin mice 1. This study suggests that endothelial cell receptors for endothelium-dependent vasodilators and Iloprost may not be homogeneously distributed or continuously expressed in thoracic aorta of heterozygous tight-skin mice 1, resulting in endothelium-dependent vasodilatation dysfunction. Moreover, because endothelium-dependent relaxation was highly dependent on nitric oxide release in heterozygous tight-skin mice 1, endothelium-dependent relaxation may differ from that of controls by increased production of nitric oxide. In turn, in heterozygous tight-skin mice 1, the resulting elevated nitric oxide levels may contribute to nitric oxide-mediated free radical endothelial cytotoxicity, although endothelium impairment may be related to other factors, particularly: Fbn-1 gene mutation and transforming growth factor-beta.
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PMID:Endothelial dysfunction in murine model of systemic sclerosis: tight-skin mice 1. 1248 43

Serum-free preservation media such as University of Wisconsin (UW) may cause tissue damage through trophic factor (TF) deprivation. This study evaluated whether the addition of TFs to UW solution improves liver graft quality after extended cold preservation time in pigs. UW solution was supplemented with epidermal growth factor, insulin-like growth factor-1, nerve growth factor-beta, bactenecin, and substance P to create TF-supplemented (TFS) UW. Orthotopic liver transplantation was performed after 18 hr of static cold storage at 4 degrees C in UW (n=7) or TFS-UW (n=7) solution. Recipients of grafts preserved with TFS-UW demonstrated significantly better 5-day survival (57%) than those preserved with UW alone (14%) (P<0.05). Adenosine triphosphate content in grafts preserved in TFS-UW was significantly higher than in grafts preserved in UW (17.4+/-5.0 vs. 4.8+/-1.2 nmol/mg protein, respectively) (P<0.05). This study showed that the addition of TFs to UW solution allowed a significant extension of cold ischemic time in pigs.
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PMID:Improved survival of orthotopic liver allograft in swine by addition of trophic factors to University of Wisconsin solution. 1474 97

Adenosine 5'-triphosphate (ATP) is a cotransmitter with classical transmitters in most nerves in the peripheral and central nervous systems, although the proportions vary between tissues and species and in different developmental and pathophysiological circumstances. There was early evidence that ATP was released together with acetylcholine (ACh) from motor nerves supplying skeletal muscle, although it was considered at the time as a molecule involved in the vesicular uptake and storage of ACh. Later it was shown that in the developing neuromuscular junction, released ATP acted on P2X receptor ion channels as a genuine cotransmitter with ACh. Adenosine triphosphate was shown to be released from sympathetic nerves supplying the guinea-pig taenia coli in 1971. Soon after, the possibility was raised that ATP was coreleased with noradrenaline from sympathetic nerves to guinea-pig seminal vesicle, cat nictitating membrane and guinea-pig vas deferens. Sympathetic purinergic cotransmission has also been demonstrated in many blood vessels. Parasympathetic nerves supplying the urinary bladder use ACh and ATP as cotransmitters; ATP acts through P2X ionotropic receptors, whereas the slower component of the response is mediated by the metabotropic muscarinic receptor. Adenosine triphosphate and glutamate appear to be cotransmitters in primary afferent sensory neurons. Adenosine triphosphate, calcitonin gene-related peptide and substance P coexist in some sensory-motor nerves. A subpopulation of intramural enteric nerves provides non-adrenergic, non-cholinergic inhibitory innervation of gut smooth muscle. Three cotransmitters are involved, namely ATP, nitric oxide and vasoactive intestinal polypeptide. In recent years, studies have shown that ATP is released with ACh, noradrenaline, glutamate, gamma-aminobutyric acid, 5-hyroxytryptamine and dopamine in different subpopulations of neurons in the central nervous system.
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PMID:Purinergic cotransmission. 1872 80