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125I-vasoactive intestinal peptide binding in human kidney
B G Charlton1, D E Neal, N L Simmons
1Department of Anatomy, University of Glasgow, UK.
Abstract:
The hypothesis that effects of vasoactive intestinal peptide (VIP) on human renal function are mediated via a specific intrarenal VIP receptor was investigated by measuring 125I-VIP binding in plasma membranes isolated from human kidney tissue excised for therapeutic reasons (transitional cell carcinoma, hypernephroma). Equilibrium binding of 125I-VIP was determined by a rapid filtration technique. Specific binding was saturable and showed evidence of both a high affinity binding site (K0.5 range 1.3-12.7 nM; Bmax range 4-56 fmol/mg) and another site of lower affinity. 125VIP binding was partially displaced by homologous peptides and by the VIP antagonist (4CL-D-Phe6,Leu17)-VIP. Distribution of 125I-VIP binding was established using autoradiography: specific binding was confined to the cortex. Such evidence of specific VIP binding, together with our previous report showing VIP stimulation of renal cortical plasma membrane adenylate cyclase, is consistent with a role for VIP in regulation of urine electrolyte composition in the human.
Insights
Researchers investigated vasoactive intestinal peptide (VIP) receptors in human kidneys. Specific VIP binding sites were found in the renal cortex, suggesting VIP plays a role in regulating urine electrolytes.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Vasoactive intestinal peptide (VIP) is implicated in regulating various physiological functions.
- Its specific role and receptor interactions within the human kidney remain incompletely understood.
Purpose of the Study:
- To investigate the presence and characteristics of specific intrarenal VIP receptors in human kidney tissue.
- To determine if VIP binding is localized to specific regions of the kidney.
Main Methods:
- Isolated plasma membranes from human kidney tissue (nephrectomy specimens).
- Quantified 125I-VIP binding using equilibrium binding assays and rapid filtration.
- Utilized autoradiography to map the distribution of specific VIP binding sites.
Main Results:
- Specific, saturable binding of 125I-VIP was observed in human kidney plasma membranes.
- Evidence of both high- and low-affinity VIP binding sites was detected.
- Autoradiography revealed that specific VIP binding is localized to the renal cortex.
- Binding was partially inhibited by homologous peptides and a VIP antagonist.
Conclusions:
- The human kidney possesses specific VIP binding sites, primarily located in the renal cortex.
- These findings support the hypothesis that VIP exerts its renal effects through dedicated intrarenal receptors.
- VIP likely plays a role in regulating human urine electrolyte composition.