Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01042 (bradykinin)
 15,585 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory mediators promote the synthesis and secretion of prostaglandin (PG) mediators in airway epithelial cells. In this study, we examined the topographic and kinetic profile of PG secretion in canine tracheal epithelial cells harvested from the tracheal posterior membrane (PM) and those obtained from the immediately anterior cartilage-associated membrane (CM). Primary cultures of tracheal epithelial cells obtained from 23 disease-free dogs were grown to confluence in serum-enriched medium. Cells then were incubated in serum-free medium for 1 h and stimulated with 10(-7) to 10(-5) M bradykinin. Baseline secretion of PGE2 was similar to both PM and CM cells; however, PM cells secreted greater concentrations in both PGI2 (measured as 6-keto-PGF1 alpha) (1,269 +/- 160 versus 775 +/- 91 pg/10(6) cells, P less than 0.01) and PGF2 alpha (436 +/- 54 versus 234 +/- 45 pg/10(6) cells, P less than 0.002) compared with CM cells. Bradykinin (BK) stimulation caused substantial secretion in less than or equal to 20 min of PGE2 and 6-keto-PGF1 alpha from PM but not CM cells: after stimulation with 10(-6) M BK, 6-keto-PGF1 alpha secretion was 348 +/- 74% in PM cells versus 157 +/- 18% of baseline secretion in CM cells (P less than 0.005); PGE2 secretion was 310 +/- 53% in PM cells versus 163 +/- 15% of baseline secretion in CM cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Topographic distribution of prostaglandin secretion caused by bradykinin in canine tracheal epithelial cells. 155 Jun 82

We examined the effects of arterial injections of bradykinin on perfusion pressure and output of PGE2 and 6-keto-PGF1 alpha in isolated kidneys of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The kidneys were perfused with Krebs' bicarbonate buffer containing phenylephrine, both with and without indomethacin (1 microgram/mL). In kidneys perfused without indomethacin, bradykinin increased the output of PGE2 and 6-keto-PGF1 alpha in the kidneys of both WKY and SHR. Bradykinin also reduced perfusion pressure, indicative of renal vasodilation. This effect in the kidneys of SHR clearly exceeded that in the kidneys of WKY. The addition of indomethacin to the perfusion media suppressed the bradykinin-induced output of PGE2 and 6-keto-PGF1 alpha without altering the vasodilatory response to bradykinin in either SHR or WKY kidneys. Hence, the kidneys of SHR demonstrated an increased vasodilatory responsiveness to bradykinin irrespective of whether the peptide stimulated prostaglandin synthesis. We conclude that the augmented responsiveness of SHR kidneys to bradykinin-induced vasodilation cannot be attributed to enhanced expression of prostaglandin-mediated mechanisms of vasodilation.
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PMID:Role of prostaglandins in the increased vascular responsiveness to bradykinin in kidneys of spontaneously hypertensive rats. 157 47

We performed these studies to determine whether sialic acid (SIA) existed in the inflammatory exudate of the carrageenin (Car)-air pouch model and to elucidate the mechanisms of the antiinflammatory action of SIA on the Car-induced edema in rat hind paws. SIA (113.20 +/- 10.73 micrograms/ml) was detected in the exudate of Car-air pouch, and the plasma SIA (660.29 +/- 29.38 micrograms/ml) in Car-air pouch rats was significantly higher than that (490.00 +/- 29.37 micrograms/ml) in control rats. SIA (300 mg/kg, s.c.) suppressed the delayed phase of Car-induced edema, and it also suppressed the edema induced by Car plus arachidonic acid, Car plus PGE2, and bradykinin plus PGE2. However, SIA did not affect the edema induced by dextran, histamine, bradykinin, and Car plus PGE1. SIA affected neither the PG production in rats nor the [3H]PGE2-receptor binding of guinea pig ileum, and SIA reduced the PGE2-induced contraction of isolated guinea pig ileum. The above results suggest that SIA induces the antiinflammatory effects via its antagonism against PGE2. Furthermore, the presence of SIA in the inflammatory exudate and the higher concentration of SIA in the plasma than in the exudate might suggest that SIA plays patho-physiologically protective roles in inflammatory states.
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PMID:[Suppressive effect of sialic acid on the prostaglandin E2-mediated edema in carrageenin-induced inflammation of rat hind paws]. 159 19

The effect of prostaglandin D2 (PGD2) on colonic ion transport was studied in the Ussing chamber. PGD2 (10(-6) M) decreased baseline short-circuit current (Isc) in two preparations of rat colon descendens, a mucosa-submucosa preparation with and a mucosa preparation without the submucosal plexus. In both preparations, PGD2 inhibited the neuronally mediated secretory responses to electric field stimulation, the sea anemone toxin ATX II, and different cholinergic agents. Unidirectional flux measurements revealed that PGD2 diminished the secretagogue-induced increase in the serosal-to-mucosal flux of Cl- and thereby inhibited net Cl- secretion. PGD2, however, had no effect on the adenosine 3',5'-cyclic monophosphate-mediated response to forskolin or vasoactive intestinal peptide or on guanosine 3',5'-cyclic monophosphate-mediated secretion induced by the heat-stable enterotoxin of Escherichia coli. The PGD2 also blocked the increase in Isc evoked by two neuronally acting inflammatory mediators, i.e., bradykinin and PGI2 in the mucosa-submucosa preparation, but had no effect on the response to PGE2. Consequently, PGD2 exerts an indirect antisecretory effect caused by an inhibition of enteric secretomotor neurons of both the submucosal and the mucosal plexus.
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PMID:Antisecretory effect of prostaglandin D2 in rat colon in vitro: action sites. 167 43

1. Mechanical activity was recorded in isolated muscle preparations from circular and longitudinal layers of gastric fundus, corpus and antrum and from the duodenum of pigs, using conventional organ bath technique. Rectangular current pulses were applied to the muscle strips for electrical field stimulation (EFS). 2. Fundic and circular corpus preparations developed a marked spontaneous tonic activity. Vasoactive intestinal polypeptide (VIP, 10(-9)-10(-7) mol l-1) inhibited this spontaneous activity. This inhibitory effect was not affected by application of tetrodotoxin (TTX) showing its myogenic nature. 3. Pretreatment of fundic and circular corpus preparations with VIP reduced the excitatory responses to substance P, bombesin, serotonin and histamine, but it had no effect on the acetylcholine (ACh)-induced tonic and phasic activity. 4. Longitudinal duodenal preparations showed purely phasic activity which was almost insensitive to VIP. In circular duodenal preparations particularly strong spontaneous tonic contractions were observed which could be inhibited by VIP. 5. Circular duodenal preparations excised 3-5 cm postpyloric had a spontaneous tone which could reach up to 80% of the maximum contractions induced by 10(-4) mol l-1 ACh. These preparations were chosen for further pharmacological studies and for experiments with EFS. VIP was the most powerful substance for the inhibition of spontaneous tone, followed by serotonin, PGE2 and bradykinin. This type of preparation exhibited particularly strong inhibitory effects to EFS; even single stimuli could induce near maximum relaxation. The inhibition induced by EFS was unaffected by treatment with ATP, guanethidine, atropine, methysergide and apamin. TTX completely abolished the EFS-induced relaxation, showing its neurogenic nature. 6. Porcine circular duodenum is a good model for studying the transmitter system of the non-adrenergic, non-cholinergic (NANC) innervation. The results are consistent with the assumption that VIP is the transmitter in this system, although the very slow time-course of the VIP-induced inhibition in comparison with the EFS-induced inhibition is not consistent with this notion.
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PMID:Responses of porcine gastric and duodenal smooth muscle to VIP. 172 15

We have developed an alternative method for examining equine tracheal epithelial arachidonic acid (AA) metabolism that utilizes strips of pseudostratified columnar epithelium attached to a layer of elastic tissue 80 to 130 microns thick. We compared the responses of this preparation with those of enzymatically dispersed suspensions of tracheal epithelium obtained from the same animal. Strips incubated with [3H]AA incorporated 40.8 +/- 3.6% of added radioactivity and released 2.55 +/- 0.23% of incorporated radioactivity when stimulated with 5 microM A23187. Values for the cell suspension were 59.6 +/- 1.6% and 1.90 +/- 0.08%, respectively. Stimulation with 50 microM histamine or bradykinin resulted in significant release of free [3H]AA only from the strips. High-performance liquid chromatography radioactivity profiles of eicosanoids released following stimulation with 5 microM A23187 demonstrated peaks that coeluted with free AA, prostaglandin (PG) E2, and PGF2 alpha for the strips, and free AA, leukotriene B4, and 5-HETE for the cell suspensions. The absence of PGE2 production by cell suspensions was confirmed by assaying immunoreactive PGE2 in supernatants from unlabeled strips and suspensions stimulated with 5 microM A23187. Epithelial strips produced 10.3 +/- 1.3 ng PGE2/ml supernatant, whereas 5 x 10(6) cells in suspension produced less than 100 pg/ml. Despite the lack of PG production by the cell suspensions, immunocytochemical staining with an anti-PGH synthase antibody demonstrated the presence of PGH synthase in epithelial cells of both preparations. These data indicate that, in contrast to epithelial cell suspensions, epithelial strips synthesize cyclooxygenase metabolites and respond to peptide agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epithelial strips: an alternative technique for examining arachidonate metabolism in equine tracheal epithelium. 172 92

Previous studies have demonstrated that bradykinin (BK) produces a sympathetically dependent plasma extravasation into the rat knee joint which is, in part, dependent upon the production of a prostaglandin. In the present study, co-administration of the specific prostaglandin, PGE2, markedly enhanced the BK-induced plasma extravasation. In this study we also report that after chemically induced sympathectomy, by chronic pretreatment with 6-hydroxydopamine (6-OHDA), both the plasma extravasation produced by BK and the enhancing effect of PGE2 are markedly attenuated. Plasma extravasation induced by PGE2 alone was small and was not significantly attenuated by sympathectomy. We conclude that BK-induced extravasation involves production of at least two sympathetic postganglionic neuron (SPGN) terminal-dependent factors, one of which is a cyclo-oxygenase product of arachidonic acid metabolism, probably PGE2, (Coderre et al., J. Neurophysiol., 62 (1989) 45-58) and another that is unidentified.
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PMID:Sympathetic neuron factors involved in bradykinin-induced plasma extravasation in the rat. 174 48

We describe a simple, noninvasive, nontraumatic and reproducible method in which the activities of bronchoactive agents may be recorded in six conscious guinea pigs simultaneously. The method involves the use of "head out" whole body plethysmographs from which respiratory rate can be recorded, by monitoring respiration-related changes in pressure within the body chamber. Exposure of a guinea pig to an aerosolised bronchoconstrictor agent causes an increase in respiratory rate, which is quantified by measuring the area under the respiratory rate curve using a purpose-built respiratory computer. This can be carried out for six animals simultaneously and independently. When exposed to a standard bronchoconstrictor aerosol challenge at intervals over a 6 hr period, the areas under the respiratory rate curves for each animal are highly reproducible. Inhalation of nebulized solutions of acetylcholine (ACh), histamine (Hist), 5-hydroxytryptamine, bradykinin, leukotriene D4 and the thromboxane A2-mimetic, U-46619, but not prostaglandin F2 alpha (PGF2 alpha) caused dose-related bronchoconstriction observed as increases in respiratory rate. In addition, salbutamol, clenbuterol, N-ethylcarboxamide adenosine (NECA) and PGE2 all inhibited ACh (1 mg mL-1) and Hist (1 mg mL-1)-induced increases in respiratory rate in a dose-related fashion. The method described, which is both noninvasive and nontraumatic, may therefore be used to quantify in the conscious guinea pig, both bronchoconstrictor and bronchodilator agents.
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PMID:A novel method for the evaluation of bronchoactive agents in the conscious guinea pig. 175 43

Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics.
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PMID:Oligonucleotides antisense to the interleukin 1 receptor mRNA block the effects of interleukin 1 in cultured murine and human fibroblasts and in mice. 183 22

Luteinizing hormone (LH) stimulates prostaglandin biosynthesis and steroidogenesis in preovulatory (PO) follicles prior to ovulation. Since the ovulatory process shares many similarities with an inflammatory reaction, mediators of the inflammatory response, such as bradykinin (BK) have been suggested to modulate the effects of LH. In the present study the effect of BK (5 microM) on: 1) prostaglandin biosynthesis (PGE2, PGF2 alpha and 6-keto-PGF1 alpha), 2) the levels of two enzymes in the cyclo-oxygenase pathway, prostaglandin endoperoxide synthase (PGS) and prostacyclin synthase (PCS), and 3) cyclic adenosine 3'5'-monophosphate (cAMP) and progesterone response of PO follicles incubated in vitro were examined. LH (0.1 microgram/ml) stimulated the accumulation of cAMP and progesterone in the medium, while BK had no effect on these parameters. BK exerted a slight stimulatory effect on PGE2, and PGF2 alpha, (p less than or equal to 0.01) but not on 6-keto-PGF1 alpha synthesis, but no changes in PGS or PCS levels could be detected. The effect of LH on prostaglandin biosynthesis was much more pronounced, with an increase of PGE2, PGF2 alpha and 6-keto-PGF1 alpha. LH also induced PGS. The combination of LH and BK did not alter these responses compared to that of LH alone. This study demonstrates that BK stimulates prostaglandin biosynthesis in PO follicles. In contrast to LH, this effect of BK does not seem to involve the adenylate cyclase system, since BK did not stimulate cAMP production. BK did not affect the levels of PGS or PCS, and the stimulatory effect of BK is suggested to involve an increase in the availability of substrate for the cyclo-oxygenase pathway.
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PMID:Regulation of prostaglandin biosynthesis by luteinizing hormone and bradykinin in rat preovulatory follicles in vitro. 185 Jan 45


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