Clearance function of type C receptors of atrial natriuretic factor in rats
The overwhelming majority of atrial natriuretic factor (ANF) receptors in kidney and vascular tissues do not mediate any of the known functional effects of the hormone. To test whether these receptors (C-ANF receptors) function as clearance receptors for circulating ANF-(1-28), we determined the effects of C-ANF-(4-23) (des(Gln18Ser19Gly20Leu21Gly22)rANF-(3-23)-NH2), a specific ligand of C-ANF receptors, on the pharmacokinetics and hydrolysis of 125I-labeled ANF-(1-28) in anesthetized rats. Radioactivity in plasma was characterized by trichloroacetic acid solubility and high-pressure liquid chromatography. C-ANF-(4-23) (1 and 10 micrograms.min-1.kg body wt-1) led to marked dose-dependent increases in initial plasma concentration of administered 125I-ANF-(1-28) and decreases in its volume of distribution at steady state (Vss), metabolic clearance rate (MCR), and appearance of hydrolytic products ((125I)monoiodotyrosine and free 125I) in plasma (Pm). At the highest dose, C-ANF-(4-23) decreased Vss from 97 +/- 12 to 36 +/- 2 ml/100 g body wt, MCR from 50 +/- 4 to 12 +/- 1 ml.min-1.100 g body wt-1, and Pm from 54 +/- 8 to 11 +/- 2% of initial plasma 125I-ANF-(1-28). The data demonstrate that C-ANF receptors are mainly responsible for the very large volume of distribution and fast MCR of ANF in the rat. In this manner, C-ANF receptors are likely to play an important role in the homeostasis of circulating ANF.
- Research Organization:
- Cornell Univ. Medical College, New York, NY (USA)
- OSTI ID:
- 6468817
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 256; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CLEARANCE
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
FUNCTIONS
GROWTH FACTORS
HYDROLYSIS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIQUID COLUMN CHROMATOGRAPHY
LYSIS
MAMMALS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEPARATION PROCESSES
SOLVOLYSIS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
VERTEBRATES