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Int Immunopharmacol. 2002 Dec;2(13-14):1771-9.

Diabetes modulates the expression of glomerular kinin receptors.

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1
Department of Medicine, Endocrinology-Diabetes-Medical Genetics, Medical University of South Carolina, 114 Doughty Street, P.O. Box 250776, Charleston, SC 29425, USA.

Abstract

The localization of kinin receptors within the kidney implicates this system in the regulation of glomerular hemodynamics. We reported that diabetes alters the activity of the renal kallikrein-kinin system, and that these alterations contribute to the development of microvascular complications of diabetes. The present study examined the influence of diabetes on the expression of glomerular B1 and B2-kinin receptors, and assessed the cellular signaling of kinin receptor activation. Rats made diabetic with streptozocin (85 mg/kg), displayed plasma glucose levels in the range of 350-500 mg/dl. At 3, 7, and 21 days, B1 and B2-kinin receptor mRNA levels were measured in isolated glomeruli from control and diabetic rats by RT-PCR. Glomeruli revealed a differential pattern of expression between the two kinin receptors. The constitutively expressed B2-receptor was increased three-fold at day 3, but returned to normal levels at day 7; whereas, the inducible B1-receptor was maximally expressed (20-fold) at day 7 and remained elevated (10-fold) at day 21. To test whether the induction of kinin receptors by diabetes translates into increased responsiveness, we measured mitogen-activated protein kinase (MAPK) phosphorylation (p42, p44) in glomeruli isolated from control and diabetic rats stimulated with B1-receptor agonist (des-Arg9-bradykinin, 10(-8) M). A three-fold increase in phosphorylation of MAPK was observed in response to B1-receptor agonist challenge in glomeruli isolated form diabetic rats compared to controls. These findings demonstrate for the first time that glomerular kinin receptors are induced by diabetes, and provide a rationale to study the contribution of these receptors to the development of glomerular injury in diabetes.

PMID:
12489791
[Indexed for MEDLINE]

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