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)

We have recently characterized a bradykinin (BK) receptor in rat renal mesangial cells (1). Activation of this receptor is associated with PGE2 release and IP3 formation suggesting involvement in cell contraction which can be linked to the control of the glomerular filtration rate (2). Whether this mesangial BK receptor is the unique glomerular BK receptor remains to be elucidated. In an attempt to answer to this question, we performed binding studies using decapsulated isolated glomeruli. Scatchard analysis of the binding data obtained with this preparation revealed the presence of two distinct B2-kinin binding sites. However, a consistent difference was observed in both the affinity and the density. We further investigated the pharmacological binding profile after an initial step of solubilization. Several experiments were performed to establish optimal conditions of solubilization. For this, different detergents such as Triton X-100, CHAPS and n-octyl beta-D glucopyranoside were tested at various concentrations, durations and temperatures of incubation. The binding was performed with two different [125I]-Tyr0-BK concentrations (0.5 and 7 nM) with either untreated decapsulated glomeruli or solubilized preparation for 45 minutes at +4 degrees C in the binding buffer containing a mixture of protease inhibitors. The greatest binding was achieved after treating glomeruli with 25 mM n-octyl beta-D glucopyranoside for 60 minutes at +4 degrees C under constant shaking. Two B2-kinin receptors of different affinities were detected. The same binding characteristics were obtained both in the 12,000 x g and 100,000 x g supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of two different affinity B2-kinin binding sites in rat glomeruli. 133 39

Prostacyclin (PGI2) plays an integral role in O2 mediation of pulmonary vasomotor tone in the fetus and newborn. We hypothesized that O2 modulates PGI2 synthesis in vitro in ovine fetal intrapulmonary arteries, with decreasing O2 causing attenuated synthesis. A decline in PO2 from 680 to 40 mmHg caused a 26% fall in basal PGI2 synthesis. PGI2 synthesis maximally stimulated by bradykinin, A23187, and arachidonic acid were also attenuated at low PO2, by 35%, 33%, and 35%, respectively. PGE2 synthesis was equally affected. In contrast, varying O2 did not alter PGI2 synthesis with exogenous PGH2, which is the product of cyclooxygenase and the substrate for prostacyclin synthetase. Prostaglandin-mediated effects of O2 on cAMP production were also examined. Decreasing PO2 to 40 mmHg caused complete inhibition of basal cAMP production, whereas cAMP production stimulated by exogenous PGI2 was not affected. In parallel studies of mesenteric arteries, PGI2 synthesis and cAMP production were enhanced at low O2. Thus, PGI2 synthesis in fetal intrapulmonary arteries is modulated by changes in O2, with decreasing O2 causing attenuated synthesis. This process is due to an effect on cyclooxygenase activity, it causes marked parallel alterations in cAMP production, and it is specific to the pulmonary circulation.
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PMID:Oxygen modulates prostacyclin synthesis in ovine fetal pulmonary arteries by an effect on cyclooxygenase. 133 69

The actions and interactions of putative mediators of inflammation, such as substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in human skin. In addition, the effects of capsaicin were examined as it is known to release (and to deplete) SP and calcitonin gene-related peptide from C-fibres. The flare evoked by bradykinin was abolished by pretreatment with lignocaine (local anesthetic), compound 48/80 (mast-cell histamine liberator), mepyramine (H1-receptor antagonist) and indomethacin (cyclo-oxygenase inhibitor) but was unaffected by atropine and ketanserin (serotonin antagonist). The weal response was not reduced by any of the drugs. The flare evoked by capsaicin was abolished by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine, atropine and ketanserin. The weal response was reduced by indomethacin. The flare response to bradykinin seems to reflect the activation of C-fibres and associated mast cells, while the flare response to capsaicin seems to reflect the activation of C-fibres only. Repeated injections of capsaicin and bradykinin produced tachyphylaxis (and cross-tachyphylaxis) and greatly reduced the SP-evoked flare. Capsaicin produced tachyphylaxis also after treatment of the skin with a local anaesthetic, suggesting that it develops independently of C-fibre impulse flow. The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the depletion of messenger peptides from the C-fibres. The flare response to SP following capsaicin- or bradykinin-induced desensitization gradually returned to normal after 5-8 weeks. The erythema evoked by PGE2 was reduced by 30% following pretreatment with lignocaine, mepyramine or compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin. 137 95

The effects of prostaglandin I2 on the discharge properties of fine articular afferents (group III and group IV fibers) in the cat were examined by extracellular recordings from single units dissected from the medial articular nerve of the knee joint. Prostaglandin I2 was applied intra-arterially close to the joint in doses of 0.3-30 micrograms per 0.3 ml bolus injection, and its effects on the spontaneous activity as well as on discharges evoked by mechanical and chemical stimulation (bradykinin) were monitored. Prostaglandin E2 was also applied and the effects of prostaglandins I2 and E2 on particular units were compared. An excitatory effect of prostaglandin I2 was observed in 49% of 37 group III and in 37% of 27 group IV units. A sensitization to passive movements of the joint occurred in 71% of 31 group III and 48% of 21 group IV units. Sixty-seven per cent of 32 units (groups III and IV) were both excited and sensitized by prostaglandin I2 to movements of 27% were sensitized but not excited. In 64% of 11 group III and 63% of eight group IV units studied the responses to bradykinin were enhanced by prostaglandin I2. Prostaglandin E2 had qualitatively similar effects as prostaglandin I2 but excited and sensitized a lower proportion of articular afferents. Forty-one per cent of the units were sensitive to both prostaglandins but 26% of the fibers were only sensitive to prostaglandin I2. None of the units was exclusively sensitive to prostaglandin E2. In general, the excitatory and sensitizing effects of prostaglandin E2 had a longer duration than those exerted by prostaglandin I2. We conclude that prostaglandin I2 increases the sensitivity to mechanical stimuli as well as to chemical stimulation by bradykinin in the majority of articular group III and group IV fibers. Moreover, in a large proportion of articular afferents, prostaglandin I2 had an excitatory effect. Thus, prostaglandin I2 may be an inflammatory mediator which is important for inflammation-evoked activity in slowly conducting afferents and it may participate in the development of arthritic hyperalgesia and pain.
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PMID:Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat's knee by prostaglandin I2. 140 58

Angiotensin II (AII) can release arachidonic acid metabolites such as prostacyclin (PGI2) and PGE2 from cells in cultures. It has recently been reported that the AT1 selective nonpeptide AII receptor antagonist losartan had similar effects. The present study was undertaken to further evaluate the effects of AII and losartan on cells which synthesize prostaglandins, including vascular smooth muscle, endothelial, and glial cells. Inhibition of specific [125I]AII binding was demonstrated in porcine smooth muscle cell (PSMC) suspensions with unlabeled AII and losartan. The IC50 values were 1.3 x 10(-9) mol/L and 7.7 x 10(-9) mol/L, respectively. PD123177 (an AT2 selective antagonist) had no effect on binding. AII produced a concentration-related increase in calcium mobilization (fura-2 fluorescence) which was blocked by losartan (IC50 = 8.4 x 10(-8) mol/L) but not by PD123177 (10(-6) mol/L). AII (10(-7) to 10(-5) mol/L) stimulated the basal release of PGI2 by 100%. This response was blocked by losartan (10(-6) to 10(-5) mol/L) but not by PD123177 (10(-6) to 10(-5) mol/L) and neither agent stimulated basal release in PSMC. Similar effects of AII and antagonists were observed upon receptor binding and PGE2 release in primary rat astrocyte (RA) cultures. AII did not release PGI2 from porcine endothelial cells, bovine pulmonary arterial endothelial cells, or rat C6 glioma cells. Losartan had no significant effect at 10(-5) mol/L. By contrast, bradykinin or the calcium ionophore A23187 dramatically increased PGI2 release in each of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AT1 receptors mediate the release of prostaglandins in porcine smooth muscle cells and rat astrocytes. 141 54

The relationship of bradykinin and cholecystokinin (CCK) to inflamed gallbladder prostanoid synthesis and release was examined in rabbits treated with common bile duct ligation (BDL) for 24 or 72 h. Gallbladders removed from control and BDL groups were incubated in oxygenated Krebs buffer at 37 degrees C (pH 7.4) for 60 min. The slices were then placed every 20 min in vials containing increasing doses of bradykinin (30-3000 ng) or CCK (30-1000 ng). Incubation fluid was analyzed by RIA for 6-keto-prostaglandin (PG)F1 alpha (PGI2 metabolite), PGE2 and thromboxane (TX) B2. Bradykinin stimulated control gallbladder 6-keto-PGF1 alpha and PGE2 release was modest. Gallbladders from 24- and 72-h BDL groups released 3- to 10-fold higher levels of 6-keto-PGF1 alpha and PGE2 (not TXB2) following bradykinin stimulation when compared to controls, which was abolished with indomethacin pretreatment. CCK did not stimulate gallbladder prostanoid release in the control or BDL groups. These data show that bradykinin and not CCK stimulated PGI2 and PGE2 release from inflamed rabbit gallbladder. Increased BDL gallbladder PGI2 release may be prolonged or augmented by bradykinin as gallbladder distention and progressive acute inflammation stimulate local bradykinin formation.
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PMID:Bradykinin and not cholecystokinin stimulates exaggerated prostanoid release from the inflamed rabbit gallbladder. 143 65

Streptozotocin-induced diabetes resulted in diminished vasodilator responses to bradykinin in the preconstricted isolated perfused kidney of the rat which were associated with decreased renal phospholipase A2 activity and reduced release of PGE2 into the renal venous effluent.
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PMID:Influence of diabetes mellitus on renal vascular responses to bradykinin. 146 37

The biologic effect of eicosanoids depends in large measure upon the relative masses in tissues of eicosanoids derived from the n-6 fatty acids, dihomogammalinolenic acid and arachidonic acid, and the n-3 fatty acid, eicosapentaenoic acid. Generation of this tissue balance is related to the relative cellular masses of these precursor fatty acids, the competition between them for entry into and release from cellular phospholipids, and their competition for the enzymes that catalyze their conversion to eicosanoids. In order to better understand these processes, we studied the cellular interactions of n-6 and n-3 fatty acids using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Unlike studies using cells with endogenous pools of n-6 and n-3 fatty acids, the use of EFD-1 cells enabled us to examine the metabolic fate of each family of fatty acids both in the presence and in the absence of the second family of fatty acids. Thus, the specific effects of one fatty acid family on the other could be directly assessed. In addition, we were able to replete the cells with dihomogammalinolenic acid (DHLA), arachidonic acid (AA), and eicosapentaenoic acid (EPA) of known specific activities; thus the masses of cellular DHLA, AA, and EPA, and their metabolites, PGE1, PGE2, and PGE3, respectively, could be accurately quantitated. The major findings of this study were: 1) n-6 fatty acids markedly stimulated the elongation of EPA to 22:5 whereas n-3 fatty acids inhibited the delta 5 desaturation of DHLA to AA and the elongation of AA to 22:4; 2) n-6 fatty acids caused a specific redistribution of cellular EPA from phospholipid to triacylglycerol; 3) n-3 fatty acids reduced the mass of DHLA and AA only in phosphatidylinositol whereas n-6 fatty acids reduced the mass of EPA to a similar extent in all cellular phospholipids; and 4) n-3 fatty acids caused an identical (33%) reduction in the bradykinin-induced release of PGE1 and PGE2, whereas n-6 fatty acids stimulated PGE3 release 2.3-fold. Together, these highly quantitative metabolic data increase our understanding of the regulation of both the cellular levels of DHLA, AA, and EPA, and their availability for eicosanoid synthesis. In addition, these findings provide a context for the effective use of these fatty acids in dietary therapies directed at modulation of eicosanoid production.
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PMID:Cellular interactions between n-6 and n-3 fatty acids: a mass analysis of fatty acid elongation/desaturation, distribution among complex lipids, and conversion to eicosanoids. 147 57

One of the major events involving inflammatory processes is the alteration of microcirculatory hemodynamics by inflammatory mediators released from tissue components. Using modern macrocirculatory techniques, 15 mu radioisotope labeled microspheres, 133Xe washout, laser Doppler flowmetry and double isotopes, 125 and 131I-albumin, and microcirculatory methods, intravital fluorescence microscopy with FITC labeled dextran, we have examined the effects of selected mediators, e.g. 5-hydroxytryptamine (5-HT), prostaglandin E2 (PG-E2), bradykinin (BK), substance P (SP), calcitonin gene related peptide (CGRP) and histamine on blood flow and vascular permeability in the pulp of experimental animals. Surprisingly, SP and CGRP caused weak albumin leakage in the pulp, while the opposite is true in high compliance tissues, such as muscles, suggesting that the vessels in a low compliance environment, such as the pulp, may not be as permeable in response to selected mediators. Intraarterial injection of 5-HT caused a strong vasoconstriction which was mediated by 5-HT1p receptor subtype. The pulpal 5-HT receptor subtype was identified by immunocytochemistry, receptor autoradiography and functional investigations. Intravital fluorescence microscopy observations of the rat incisor preparation showed that histamine, BK and PGE2 increased permeability, whereas isoproteranol caused partial inhibition of the BK-induced increase. In an induced pulpal inflammation model using plaque extract, blood flow increased over 40% in the moderately inflamed pulp, which demonstrated severe vasodilation and polymorpholeukocyte accumulation. In the partially necrotic pulp, blood flow decreased nearly 35%. Results of this study clearly show that there is a high structural/functional correlation in pulpal microcirculation in inflammation. As demonstrated in this presentation, the effects of inflammatory mediators on pulpal microcirculatory hemodynamics are complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp. 150 95

Bradykinin (BK) is a potent algesic compound. Therefore, we hypothesized that BK, acting as a peripheral noxious stimulus, would attenuate or inhibit responses to another noxious stimulus. When administered intravenously (i.v.) to rats lightly anesthesized with pentobarbital, BK produced a dose-dependent (12-144 micrograms/kg) inhibition of the nociceptive tail-flick (TF) reflex. BK also produced a dose-dependent decrease in mean arterial blood pressure, a subsequent increase in heart rate and an increase in the rate of respiration. The latency to the maximal effect of BK on the TF reflex was 10 s and was occasionally preceded by pseudoaffective responses at doses greater than 48 micrograms/kg BK. Neonatal treatment with capsaicin (50 mg/kg, subcutaneous) significantly attenuated BK-produced inhibition of the TF reflex indicating that BK was acting via peripheral afferents to inhibit the TF reflex. Reversible cold block or complete spinal transection at a low thoracic level (T9-12), but not reversible cold block at a high cervical level (C1-2), significantly attenuated BK-produced inhibition of the TF reflex, suggesting that BK activates afferents which enter the spinal cord between C2 and T9. Pretreatment with intrathecally administered phentolamine (30 micrograms), an alpha-adrenoceptor antagonist, or methysergide (30 micrograms), a non-selective serotonin receptor antagonist, did not alter BK-produced inhibition of the TF reflex, further supporting the absence of activation of descending systems from the brainstem by i.v. BK. While coadministration of PGE2 and BK significantly potentiated BK-produced inhibition of the TF reflex, neither bilateral removal of the stellate ganglion nor bilateral cervical vagotomy significantly affected the inhibitory action of i.v. BK on the TF reflex. These results suggest that i.v. BK inhibits the nociceptive TF reflex by activation of capsaicin-sensitive visceral afferents entering the spinal cord between C2 and T9.
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PMID:Bradykinin modulation of a spinal nociceptive reflex in the rat. 151 Dec 77


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