Bradykinin-induced in vitro contraction of rat mesangial cells via a B2 receptor type

Bascands, Jean Loup; Pécher, Christiane; Bompart, Guy; Rakotoarivony, J; Tack, Jan; Girolami, Jean-Pierre

doi:10.1152/ajprenal.1994.267.5.f871

Cited by 14 publications

(15 citation statements)

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“…A comparable bradykinininduced decrease in pre-and postglomerular arteriolar resistance has, however, been found in rats [18] and dogs [19]. Also it cannot be excluded that blockade of the bradykinininduced mesangial cell contraction contributed to the rise in FF in our model [20].…”

Section: Discussionsupporting

confidence: 68%

Endogenous Bradykinin Regulates Renal Function in the Newborn Rabbit

Tóth-Heyn

Guignard²

1998

Neonatology

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The developmental changes in the activity of the renal kallikrein-kinin system (KKS) are related to the hemodynamic changes occurring in the neonatal kidney. In order to clarify the functional importance of the renal KKS in the developing kidney, the effect of the bradykinin B2 receptor antagonist HOE-140 was investigated in newborn rabbits. Effective blockade of bradykinin effect by HOE-140 was demonstrated in 10 rabbits. In 10 additional animals the subcutaneous injection of 300 µg/kg HOE-140 resulted in an increase in renal vascular resistance with a consequent decrease in renal blood flow. Glomerular filtration rate did not change significantly, while the filtration fraction rose, indicating preferential efferent arteriolar constriction. Urine flow rate increased as well as the fractional excretion of potassium. No change in sodium excretion was observed. The present data suggest a regulatory role for the renal KKS in the immature kidney under basal conditions. By inducing predominant efferent arteriolar vasodilation, the KKS appears to play a key role in regulating the neonatal glomerular microcirculation. This is in sharp contrast with the mature kidney, where the KKS predominantly acts on tubular function as a diuretic-natriuretic factor.

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Section: Discussionsupporting

confidence: 68%

Endogenous Bradykinin Regulates Renal Function in the Newborn Rabbit

Tóth-Heyn

Guignard²

1998

Neonatology

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“…For immunoprecipitation of the receptor we applied antiserum AS346 which has been raised against a peptide derived from the COOH terminus of the B 2 wt (positions 329 to 364) (21). In 35 S labeling experiments (Fig. 4d), immunoprecipitation of B 2 wt resulted in a diffuse band of 60 -100 kDa that was superimposable with the immunoreactive band found in 32 P labeling experiments (Fig.…”

Section: Internalization Of [mentioning

confidence: 53%

Bradykinin-induced Internalization of the Human B2Receptor Requires Phosphorylation of Three Serine and Two Threonine Residues at Its Carboxyl Tail

Pizard¹,

Blaukat²,

Müller‐Esterl³

et al. 1999

Journal of Biological Chemistry

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Mutants with a markedly reduced internalization potential failed to produce BK-induced receptor phosphorylation suggesting that phosphorylation may be involved in receptor internalization. The mutagenesis approaches converged at the conclusion that three serines in positions 339, 346, and 348 and two threonines in positions 342 and 345, contained in a sequence segment that is highly conserved between species, have a critical role in the liganddependent internalization and phosphorylation of kinin receptors and can intervene in these processes in an alternative manner. However, mutants lacking these residues were still sensitive to dominant-negative forms of ␤-arrestin and dynamin, suggesting the existence of additional receptor structure(s) involved in the receptor sequestration through clathrin-coated vesicles.

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“…Mesangial cells are potential mediators of the glomerular damage that we report in this article because they express the B2 receptor and respond in various ways to bradykinin (17,18). However, the increase in interstitial fibrosis that we find in the diabetic mice lacking the B2 receptor suggests that the increased nephropathy in the double mutants must involve events additional to those mediated by mesangial cells.…”

Section: Discussionmentioning

confidence: 66%

Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor

Kakoki

Takahashi

Jennette

et al. 2004

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

123

105

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Type I human diabetics and streptozotocin-induced diabetic mice with higher genetically determined levels of angiotensin-converting enzyme have an increased risk of developing nephropathy. However, previous experiments in mice and computer simulations indicate that modest increases in angiotensin-converting enzyme have minimal effects on blood pressure and angiotensin II levels, although bradykinin decreases significantly, inferring that bradykinin is critical for protecting the kidney in diabetics. Here, we confirm this inference by demonstrating that Akita diabetic mice lacking the bradykinin B2 receptor develop overt albuminuria, excreting the equivalent of >550 mg͞day albumin in humans, which contrasts with the microalbuminuria (equivalent to <150 mg͞day) seen in their simply diabetic littermates. The overt albuminuria is accompanied by a marked increase in glomerular mesangial sclerosis. The importance of bradykinin demonstrated here bears strongly on how current drugs reduce diabetic nephropathy and suggests that B2 receptor-specific agonists merit consideration in this context. maturity onset diabetes of the young ͉ albuminuria ͉ glomerulosclerosis D ifferences in expression of the gene coding for angiotensinconverting enzyme (ACE), such as are observed in humans in relation to the insertion͞deletion polymorphism in the ACE gene (1) and in mice with different numbers of the gene (2), have minimal effects on angiotensin II (ANGII) levels because the steady-state concentrations of the products of ACE are less sensitive to modest changes in the activity of the enzyme than the concentrations of its substrates. Thus, our recent computer simulations (3, 4) and accompanying experimental data indicate that a 50% increase in ACE causes a Ͻ5% increase in steadystate ANGII levels but close to a 20% decrease in bradykinin levels. Hence, our inference that the causative link between genetic differences in ACE expression and diabetic nephropathy (5, 6) is likely to be mediated by the ACE substrate bradykinin. To test this inference, we have combined the following two mutations: a dominant mutation that leads to maturity onset diabetes, Akita (7), resulting from an amino acid change in the insulin 2 gene (Ins2 C96Y ) (8), and a recessive knockout mutation (Bdkrb2 Ϫ ) (9) in the gene coding for the bradykinin B2 receptor, the receptor predominantly expressed in the normal kidney. Materials and MethodsAnimals. Animals were purchased from The Jackson Laboratory and bred in our mouse facility. The mice having the null allele for the bradykinin B2 receptor (9) were backcrossed to wild-type C57BL͞6J at least six times before mating to mice heterozygous for the Akita mutation (Ins2 ϩ/C96Y ) (7), which already have the C57BL͞6J genetic background. All experiments were conducted in accordance with the guidelines of the University of North Carolina Institutional Animal Care and Use Committee. Blood pressures were measured as described (2). Plasma glucose levels were determined with the glucose-oxidase method (Wako, Richmond, VA)....

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Bradykinin-induced in vitro contraction of rat mesangial cells via a B2 receptor type

Cited by 14 publications

References 0 publications

Endogenous Bradykinin Regulates Renal Function in the Newborn Rabbit

Endogenous Bradykinin Regulates Renal Function in the Newborn Rabbit

Bradykinin-induced Internalization of the Human B2Receptor Requires Phosphorylation of Three Serine and Two Threonine Residues at Its Carboxyl Tail

Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor

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