UNIPROT:P01042 - FACTA Search

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Query: UNIPROT:P01042 (bradykinin)
15,585 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Otitis media with effusion (OME) is a very common pediatric disease of unknown etiology which sometimes leads to chronic recurrent OME. The author investigated 90 secretions (39 serous/51 mucous) of 61 children whose ages ranged from 1 to 14 years (mean = 4.9 +/- 2.2) for correlations of Immunoglobulins A, E, G, M, the complement system and mediators of inflammation: histamine, Bradykinin, PGE2 and LTC4. A highly significant increase in IgA and IgG and a decrease in IgM and IgE were found in the secretions as compared to the serum concentrations. These data support the hypothesis that there is an independent mucosal immune response in the middle ear. The protein concentration was significantly higher in the mucous than in the serous secretion; for the other parameters determined only a slight tendency toward higher levels in serous secretions was found. There was a slight positive correlation between IgA and IgG in serum, and in particular in the serous secretions. A slightly negative correlation between IgM and IgE was found only in serum. The secretion showed highly significant correlations between the following: IgG:IgM, IgG:IgA, IgA:IgM, IgG:Kinin, C3c:Kinin and lg Histamine:lg PGE2. The correlations were stronger in serous than in mucous secretions. Only in mucous secretions there were any significant correlations between IgE:IgG, lg IgE:lg Kinin, and a negative correlation between IgE:C3c. Serous and mucous secretions represent different stages of inflammation. The kallikrein kinin system, complement-system, and the arachidonic acid cascade, especially the cyclo-oxygenase pathway, play a role in OME. Bradykinin showed a connection between the activated complement system and the immune system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Correlation of immunoglobulins, the complement system and inflammatory mediators with reference to the pathogenesis of serous otitis media]. 235 13

The effects of SQ 29,548 on vasoconstrictor responses were investigated in the feline mesenteric vascular bed. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in mesenteric arterial perfusion pressure. After administration of SQ 29,548, 0.5 mg/kg i.v, vasoconstrictor responses to U46619 and U44069 were reduced markedly whereas responses to prostaglandin (PG) F2 alpha, angiotensin II, vasopressin and BAY K 8644, an agent which enhances calcium entry, were not altered. The duration of the TXA2 receptor blockade was greater than 2 h and SQ 29,548 had no significant effect on mesenteric vasodilator responses to PGE2, isoproterenol, nitroglycerin, acetylcholine or bradykinin. SQ 29,548, at a dose of 0.5 mg/kg i.v., significantly reduced the response to TXB2, which had modest vasoconstrictor activity in the mesenteric vascular bed. However, when the dose of SQ 29,548 was reduced to 0.05 mg/kg i.v., responses to TXB2 were not altered, whereas responses to U46619 were significantly decreased. SQ 29,548 had no significant effect on vasoconstrictor responses to norepinephrine or to sympathetic nerve stimulation. The TXA2 receptor antagonist blocked the vasoconstrictor component of the biphasic response to the PG precursor, arachidonic acid, and the endoperoxide, PGH2. The results of these studies suggest that SQ 29,548 is a specific TX receptor antagonist in the mesenteric vascular bed, that the vasoconstrictor component of the biphasic response to arachidonic acid and PGH2 is due to formation of TXA2, and that endogenously formed TXA2 does not modulate adrenergic responses in the mesenteric circulation of the cat.
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PMID:Influence of SQ 29,548 on vasoconstrictor responses in the mesenteric vascular bed of the cat. 236 76

1. An epithelium-derived inhibitory factor (EpDIF) released by guinea-pig tracheal epithelium was evaluated in a co-axial bioassay system consisting of an epithelium-intact guinea-pig tracheal tube surrounding endothelium-denuded rat aortic strip. 2. Histamine and several muscarinic agonists induced concentration-dependent relaxation of phenylephrine-contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea-pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 microM), 1,1-dimethyl-4-phenylpiperazinium (DMPP) (25 microM), calcium ionophore A23187 (0.5 microM), bradykinin (0.05-0.5 microM), substance P (5 microM), platelet activating factor (PAF, 1-100 nM), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1-10 nM) as well as hyperosmotic stimuli. 3. Prostaglandin E2 (PGE2) induced concentration-dependent contraction of endothelium-denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 microM) the cyclo-oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P-450 inhibitors metyrapone (1 mM) and SKF 525A (25 microM). This suggests that EpDIF is neither a prostanoid nor a cytochrome P-450 metabolite of arachidonic acid. 4. The soluble guanylate cyclase inhibitor, methylene blue (50 microM), caused small but significant increases in the potencies of both histamine and methacholine in co-axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The beta-adrenoceptor antagonist, (-)-propranolol (1 microM), and the PAF-receptor antagonist, WEB 2086 (50 microM), also failed to alter significantly EpDIF-modulated relaxations. These data suggest that EpDIF is neither a stimulant of fiadrenoceptors nor of PAF receptors. 5. The present study provides some evidence that this vascular smooth muscle-sensitive EpDIF may not be related to the putative EpDIF previously hypothesized to modulate directly spasmogen-induced airway smooth muscle tone.
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PMID:Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF). 239 Jun 83

The active sequence in bradykinin (BK) responsible for PGE-aided inhibition of CSF-1-stimulated clonal proliferation of murine mononuclear phagocyte progenitors was determined. In total marrow cultures, BK and (D-Phe7)-BK, a specific BK antagonist, inhibited colony formation by CSF-1 responsive precursors that require two signals, CSF and LPS, for clonal proliferation. (Lys1)-BK, an inactive BK analogue with Lys substituted for the amino-terminal Arg, was inactive. Arg-Pro-Pro-Gly, the amino-terminal tetrapeptide fragment of BK, was fully capable, on a molar basis, of replacing either BK or (D-Phe7)-BK as an inhibitor. Bk, (D-Phe7)-BK, and Arg-Pro-Pro-Gly were not inhibitory for colony formation in cultures containing indomethacin or in cultures depleted of adherent marrow cells. However, in these cultures addition of 10(-9) M PGE2 fully restored inhibition of two-signal-dependent colony formation. PGE2-dependent inhibition by the three peptides was equivalent on a molar basis indicating that Arg-Pro-Pro-Gly contains the sequence responsible for this inhibitory effect of BK and is sufficient to exert PGE-dependent inhibition of two-signal-dependent colony formation. The two-signal-dependent progenitors appear to be in transition to CSF competence suggesting that BK and PGE produced in an hematopoietic environment may act together to limit the production of new macrophages by inhibiting progenitors in transition to CSF competence.
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PMID:Bradykinin sensitization of colony-stimulating factor-1-responsive murine marrow progenitors to prostaglandin E. A property of the amino-terminal tetrapeptide fragment. 240 68

The rat adipocyte contains two separate mechanisms for prostaglandin (PG) production. Norepinephrine stimulates prostacyclin (PGI2) and PGE2 production and triglyceride lipolysis in isolated rat adipocytes. In contrast, the vasoactive peptides angiotensin II, vasopressin, and bradykinin stimulate PGI2 production, but not PGE2 production or triglyceride lipolysis, in these cells. In this study, we characterized the two separate mechanisms of PG production with respect to the time course, the role of cAMP, the identity of the adrenergic receptor, and the effects of insulin and glucocorticoids. Angiotensin II stimulated PGI2 production rapidly (at 5 min) and independently of cAMP. beta-Adrenergic stimulation with isoproterenol produced a rapid 11-fold increase in the cAMP concentration and stimulated PGI2 production more slowly (at 120 min). The phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (0.2 and 0.5 mM) and the adenylate cyclase activator forskolin (10 microM) also stimulated cAMP production rapidly and PGI2 production more slowly. 1-Methyl-3-isobutylxanthine (5.0 mM) further stimulated cAMP levels, but prevented the increase in PGI2 production and blunted the increase in glycerol release seen at lower concentrations. beta-Adrenergic blockade with propranolol or timolol completely inhibited the norepinephrine- or isoproterenol-stimulated production of PGI2 and triglyceride lipolysis, respectively. Insulin selectively inhibited isoproterenol-stimulated PGI2 production and triglyceride lipolysis at physiological concentrations, but had no effect on angiotensin II-stimulated PGI2 production. In contrast, dexamethasone inhibited PGI2 production induced by both isoproterenol and angiotensin II. We conclude that: angiotensin II stimulates PGI2 production rapidly and independently of cAMP, but isoproterenol stimulates PGI2 production more slowly, an effect that is cAMP dependent; insulin inhibits the cAMP-dependent beta-adrenergic stimulation of PGI2 production (and triglyceride lipolysis), but not the cAMP-independent angiotensin II-induced stimulation of PGI2 production (this suggests that the former effect is mediated by a decrease in cAMP levels in the adipocyte); and dexamethasone inhibits both mechanisms of PGI2 production. Both mechanisms of PGI2 production by rat adipocytes are exquisitely sensitive to hormonal regulation.
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PMID:Prostacyclin production by isolated rat adipocytes: evidence for cyclic adenosine 3',5'-monophosphate-dependent and independent mechanisms and for a selective effect of insulin. 242 31

The eicosanoid profiles, sites of production, and response to bradykinin stimulation were determined in rabbit ileum and its various components by radioimmunoassay of various prostanoids and 5-lipoxygenase products in the incubation media. The profile of eicosanoid synthesis and secretion by the epithelial cell fraction was PGF2 alpha greater than 6-keto-PGF1 alpha greater than dihydro-keto-PCM = PGE2 greater than TxB2 much greater than 5-HETE greater than LTB4 and by the deepitheliated ileum was PGE2 = 6-keto-PGF1 alpha greater than PGF2 alpha greater than dihydro-keto-PGM greater than TxB2 much greater than LTB4 greater than 5-HETE. PGD2 was not sought in these studies. Rates of eicosanoid production by the deepitheliated ileum were over 200 times that of the epithelial cells. The epithelial cells accounted for 67% of the protein but only 0.2% of the PGE2 produced, while the lamina propria and submucosa contained only 12-30% of the protein but produced 80-90% of the PGE2. Bradykinin (1 microM), A23187 (10 microM), arachidonic acid (20 microM), and melittin (0.7 microM) stimulated PGE2 and 6-keto-PGF1 alpha production by 200% in deepitheliated (or subepithelial) ileum, but bradykinin failed to stimulate production of any eicosanoid by the epithelial cell fraction. Thus the subepithelium (predominantly the lamina propria) is the major eicosanoid producer of rabbit ileum and is the major site of bradykinin-stimulated eicosanoid synthesis and secretion. Eicosanoids released from subepithelial components may be important regulators of epithelial function.
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PMID:Bradykinin-stimulated eicosanoid synthesis and secretion by rabbit ileal components. 243 46

By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.
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PMID:Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin. 244 59

Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint.
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PMID:Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in response to bradykinin. 247 45

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the capacity of PGE2 synthesis in cultured renal papillary collecting tubule cells from young (4-week-old) and aged (16-week-old) SHR and control Wistar-Kyoto rats (WKY). Basal levels of PGE2 synthesis were lower in young SHR cells than in WKY cells (p less than 0.001). Arachidonic acid-stimulated PGE2 synthesis, however, had a slight tendency to be higher in SHR cells than in WKY cells. Bradykinin- and A23187-stimulated PGE2 synthesis were similar in both strains. Basal levels of cyclic AMP were also lower in young SHR cells than in WKY cells (p less than 0.001), but the cAMP response to exogenous PGE2 was equal between the strains. In papillary collecting tubule cells from aged rats, basal levels of PGE2 and cyclic AMP as corrected for cellular protein were significantly lower than those in young rats, but there was no difference between the strains. Urinary excretion of PGE2 and thromboxane B2 was equal in aged SHR and WKY. These results suggest that papillary collecting tubule of young SHR and WKY may differ in the metabolism of PGE2 and cyclic AMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.
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PMID:PGE2 synthesis in cultured renal papillary collecting tubule cells from young and aged spontaneously hypertensive rats. 248 50

The microvasculature is known to be a source of a number of vasoregulatory prostanoids. In the kidney, these prostanoids have been proposed to influence vascular, tubular, and glomerular function. A rapid method for isolation of large numbers of preglomerular renal microvessels (interlobular arteries and afferent arterioles) from the rabbit kidney has recently been developed in this laboratory. In the current report, we describe methods to culture endothelial cells derived from these isolated renal microvessels. Endothelial cells in primary and continuous cultures were grown in monolayers on culture dishes and plates. These cells demonstrated morphology consistent with that described for other endothelial cells in culture including the presence of Weibel-Palade bodies as seen by electron microscopy. The presence of factor VIII immunofluorescence and angiotensin converting-enzyme activity was also observed. The cultured endothelial cells synthesized a number of common prostanoids under in vitro conditions and the hierarchy of biosynthesis was PGE2 greater than PGF2 alpha greater than PGI2 greater than TxA2. The ratio of the in vitro biosynthesis of PGI2:PGE2 was approximately 1:5, as compared with a 3-5:1 ratio seen in freshly isolated intact microvessels. Prostanoid biosynthesis increased in the cultured endothelial cells in the presence of arachidonic acid (1 and 10 microM), A23187 (10 microM), thrombin (5 U/ml), or bradykinin (1 microM) and decreased with mepacrine (10 microM)-or indomethacin (100 microM), suggesting that these cells were metabolically responsive to a variety of prostanoid stimulators and inhibitors. In summary, endothelial cells can be cultured from freshly isolated preglomerular renal microvessels and have the ability to produce a number of vasoregulatory prostanoids under in vitro conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PGI2 is not a major prostanoid produced by cultured rabbit renal microvascular endothelial cells. 249 67

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