Fate of recombinant human renin administered exogenously to anesthetized monkeys
Highly purified recombinant human renin (rh-renin), synthesized by Chinese hamster ovary cells, was labeled with iodine-125 and was given intravenously to pentobarbital-anesthetized common marmosets (Callithrix jacchus) to study the fate of the circulating renin. Specific anti-rh-renin antiserum was used to identify the 125I-rh-renin. Plasma disappearance of the exogenously administered 125I-rh-renin in marmosets (n = 6) showed two exponential components, with a half-life of 12.1 +/- 1.9 minutes for the rapid component and 120.3 +/- 16.4 minutes for the slow component. The metabolic clearance rate was 1.17 +/- 0.26 ml/min/kg. Thirty minutes after the injection of 125I-rh-renin, 43.1 +/- 0.9 and 3.5 +/- 0.5% of the injected dose had distributed to the liver and the kidneys, respectively. With time, the accumulated 125I-rh-renin in the liver and kidneys decreased. The accumulation of 125I-rh-renin was less than 1% of the dose injected in other organs such as lungs, heart, spleen, adrenal glands, testes, and ovaries. Analysis of liver and kidney extracts by high performance liquid chromatography at 30 and 120 minutes indicated that immunoreactive 125I-rh-renin decreased with time and was accompanied by an increase in nonimmunoreactive degradation products of a low molecular weight. The incubation of 125I-rh-renin with monkey or human plasma at 37 degrees C did not degrade the labeled renin. Therefore, rh-renin was rapidly cleared from the circulation by the liver and the kidney.
- Research Organization:
- Osaka City Univ., Medical School (Japan)
- OSTI ID:
- 6558614
- Journal Information:
- Hypertension (Dallas); (United States), Vol. 12:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
RENIN
METABOLISM
ANESTHESIA
BIOLOGICAL HALF-LIFE
BLOOD PRESSURE
CLEARANCE
INTRAVENOUS INJECTION
IODINE 125
LIQUID COLUMN CHROMATOGRAPHY
MONKEYS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HYDROLASES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NONSPECIFIC PEPTIDASES
NUCLEI
ODD-EVEN NUCLEI
PEPTIDE HYDROLASES
PRIMATES
RADIOISOTOPES
SEPARATION PROCESSES
VERTEBRATES
550501* - Metabolism- Tracer Techniques