Characterization of soluble bradykinin receptor-like binding sites

Fredrick, Mark J.; Odya, Charles E.

doi:10.1016/0014-2999(87)90129-4

Cited by 18 publications

(5 citation statements)

References 17 publications

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“…Kinin receptor heterogeneity in the guinea-pig ileum has also been proposed by Innis et al (1981), based on correlations between the rank orders of potency of kinin related peptides in competing for Bk-binding sites and in promoting contraction. These authors also provided evidence for the occurrence of a single type of kinin receptor in the rat myometrium, a view that has received increasing support (Odya et al, 1980;Yasujima et al, 1982;Frederick et al, 1984;Frederick & Odya, 1987). Taken together, these studies strongly indicate that kinin receptors can vary between tissues.…”

Section: As Shown Inmentioning

confidence: 83%

The competitive antagonistic effect of compounds from Mandevilla velutina on kinin‐induced contractions of rat uterus and guinea‐pig ileum in vitro

Calixto

Pizzolatti

Yunes

1988

British J Pharmacology

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1 Pure non-peptide compounds obtained in crystal form from the crude extract of the plant Mandevilla velutina (Apocynaceae) were analysed for their antagonistic effects on rat uterine and guineapig smooth muscle contractions induced by bradykinin (Bk), lisyl-bradykinin (L-Bk), acetylcholine (ACh), oxytocin and histamine, in vitro. 3 In the guinea-pig ileum, both MV 8608 and MV 8612 (5 to 20 pgml-1), produced concentration-dependent rightward displacements of the concentration-response curve to Bk (0.1 to 1000 nM) when the experiments were performed in the presence but not in the absence of atropine (2.5 pM). However, in contrast to the result obtained in the rat uterus, compound MV 8608 also caused a significant reduction of the maximal response to Bk. The Schild plot for compound MV 8612 was linear (correlation close to unity) and furnished a nominal pA2 value (g ml 1) of 5.3 and a slope not different from unity.4 In rat uterine muscle, compounds MV 8608 and MV 8612 at concentrations producing marked rightward displacements of the kinin concentration-response curves (10 and 20Ygml 1), did not influence the uterine contractile response to oxytocin or ACh, indicating some selectivity towards kinin receptors. Similarly, compound MV 8612 (10 and 20 ygml 1) did not interfere with the sensitivities or the maximal responses to ACh and histamine in the guinea-pig ileum, whereas compound MV 8608 (10 and 20ug ml-1) caused a slight reduction of ACh-and histamine-induced maximal contractions, allied to decrease of the sensitivity to histamine at concentrations of 20pgml-1 or more.5 These results extend our previous data, indicating the existence of several non-peptide compounds in the crude extract of Mandevilla velutina that act as simple, competitive, selective and reversible kinin receptor antagonists in the rat isolated uterus and guinea-pig ileum smooth muscle.

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Section: As Shown Inmentioning

confidence: 83%

The competitive antagonistic effect of compounds from Mandevilla velutina on kinin‐induced contractions of rat uterus and guinea‐pig ileum in vitro

Calixto

Pizzolatti

Yunes

1988

British J Pharmacology

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“…B2 kinin receptors in particulate and CHAPS-solubilized preparations of bovine myometrium have been studied by others using 1251I-Tyr-BK [33][34][35]. These studies focused primarily on the pharmacological characteristics of-the receptors and did not address either receptor heterogeneity or guanine-nucleotidesensitivity.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin recognizes different molecular forms of the B2 kinin receptor in the presence and absence of guanine nucleotides

Mathis

Leeb-Lundberg

1991

Biochemical Journal

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We have previously reported that [3H]bradykinin [( 3H]BK) identifies high- and low-affinity B2 kinin receptor sites in bovine myometrial membranes which are sensitive and insensitive respectively to guanine nucleotides. Here we show that these receptor-binding sites are solubilized by the detergent CHAPS. Equilibrium binding in soluble preparations revealed that [3H]BK identified a maximal number of binding sites (Bmax) of 1119 +/- 160 fmol/mg of protein, with an equilibrium dissociation constant (KD) of 314 +/- 70 pM and with a typical B2 kinin receptor specificity. Dissociation of equilibrium binding was biphasic. In the presence of the GTP analogue guanosine 5'[beta gamma-imido]triphosphate (Gpp[NH]p, [3H]BK bound to the soluble receptors with a KD of 929 +/- 129 pM and a Bmax. of 706 +/- 38 fmol/mg of protein. The Gpp(NH)p-promoted decrease in the apparent affinity and Bmax., which was half-maximal at 0.5 microM, was due at least in part to an increase in the dissociation rate of the slowly dissociating component of the equilibrium binding. Recoveries of guanine-nucleotide-sensitivity and of rapidly and slowly dissociating binding components were essentially identical, whether or not the receptor had been occupied by an agonist before solubilization. Sucrose-density-gradient sedimentation profiles revealed that [3H]BK recognized two different molecular forms of the receptor in the absence or presence of guanine nucleotides. These results provide for the first time direct evidence that guanine nucleotides promote a change in the structure of the B2 kinin-receptor complex. We propose that this structural change is due to dissociation of a guanine-nucleotide-regulatory (G-)protein.

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“…Many BK B2 receptors expressed in other tissue systems and immortalized cell lines appear to correspond to one of the three affinity forms identified in WI-38 cells (5)(6)(7)(12)(13)(14)(15). To understand the basis of this diversity, mAbs specific for different affinity forms of BK receptors were obtained by immunizing with membranes from WI-38 cells concurrently expressing I-and L-affinity receptors and screening for mAb inhibition of B2 BK-mediated PGE2 production in the HSDMLCj tumor cell line.…”

Section: Methodsmentioning

confidence: 99%

Human bradykinin B2 receptors isolated by receptor-specific monoclonal antibodies are tyrosine phosphorylated.

Jong¹,

Dalemar²,

Wilhelm³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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We report the immunoaffinity isolation of bradykinin B2 receptors in a tyrosine-phosphorylated state from WI-38 human lung fibroblasts. We generated six monoclonal antibodies directed against B2 bradykinin receptor biologic activity mediating prostaglandin E2 production in WI- Bradykinin (BK), Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, is a multifunctional mediator that aids in maintaining tissue homeostasis and plays a key role in events accompanying inflammation. BK is proteolytically generated from kininogen precursors in circulation and interstitial tissue fluids; its local concentration is rapidly increased upon tissue injury. BK receptors belonging to the guanine nucleotide-binding protein (G-protein)-coupled family trigger neuronal transmission of pain or irritant messages, enhancement of vascular permeability, and altered vasomotor tone that are prominent features of the inflammatory process. BK action on these same receptors also regulates mitogenesis and protein production in fibroblasts, initiating repair steps that restore normal tissue form and function following injury (1-4).We (1) previously demonstrated that IMR-90 human lung fibroblasts sequentially mobilize BK B2 subtype receptors of Kd = 2.5-5 nM and 44 nM that mediate prostaglandin E2 (PGE2) production, upon progression through their finite life span in vitro. Further information is needed at the cellular and molecular level to elucidate the nature of BK B2 receptors and the means by which cells can express diverse receptor forms. Although recent cloning of two BK receptors has disclosed their primary sequences (5-7), the molecular structure of the protein as expressed in intact cells remains uncharacterized. We have generated monoclonal antibodies (mAbs) that distinguish the BK receptors of Kd = 5 nM and 44 nM in human lung fibroblasts and have used them to isolate the receptor protein and to demonstrate that it containsThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. phosphorylated tyrosine, which may serve a regulatory function. We also show that tyrosine kinase activity is essential for BK-mediated PGE2 production. These mAbs will allow us to explore the role of BK receptors in the growth and development of fibroblasts and in these cells' participation in onset and/or propagation of the injury/inflammation response. 4°C was covalently crosslinked to receptors with 0.4 mM disuccinyl suberimidate (Pierce) at 4°C for 20 min. After quenching with 150 mM Tris (pH 8), cells were solubilized 2.5 min in 400 ,ul of 1% Triton X-100 or 12 mM 3-[(3-cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS)/ 0.5% digitonin (CD) in 0.15 M NaCl/15 mM Tris Cl, pH 7.4, containing protease inhibitors (100 ,uM phenylmethanesulfonyl fluoride, 16.8 uM leupeptin, chymostatin at 4 ,ug/ml, 5.8 ,tM pepstatin, 6.6 ;LM antipain, 0.08 trypsin inhibitor unit of aprotinin per ml, 10 mM benzamidine, soybe...

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Characterization of soluble bradykinin receptor-like binding sites

Cited by 18 publications

References 17 publications

The competitive antagonistic effect of compounds from Mandevilla velutina on kinin‐induced contractions of rat uterus and guinea‐pig ileum in vitro

The competitive antagonistic effect of compounds from Mandevilla velutina on kinin‐induced contractions of rat uterus and guinea‐pig ileum in vitro

Bradykinin recognizes different molecular forms of the B2 kinin receptor in the presence and absence of guanine nucleotides

Human bradykinin B2 receptors isolated by receptor-specific monoclonal antibodies are tyrosine phosphorylated.

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