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Renal glutaminase adaptation and ammonia excretion in infant rats
Insights
Developing rats show low ammonia excretion during acidosis, but enzyme adaptation, specifically phosphate-dependent glutaminase (PDG), increases excretion with repeated acid exposure. This adaptive response is crucial for infant kidney function.
Area of Science:
- Renal physiology
- Developmental biology
- Biochemistry
Background:
- Infant rats exhibit a limited capacity for ammonia excretion in response to acidosis.
- Understanding the mechanisms behind this limited response is crucial for pediatric nephrology.
Purpose of the Study:
- To investigate the role of enzyme adaptation in regulating renal ammonia excretion during acidosis in developing rats.
- To elucidate the specific enzymes involved in the adaptive response of ammonia excretion in infant rats.
Main Methods:
- Developing rats (7-12 days old) were administered an acidifying salt (NH4Cl) to induce acidosis.
- Renal ammonia excretion and phosphate-dependent glutaminase (PDG) activity were measured.
- The effect of actinomycin D on PDG activity and ammonia excretion was assessed.
Main Results:
- Repeated administration of NH4Cl significantly increased renal ammonia excretion and PDG activity in infant rats.
- PDG activity increased from 36% to 79% of adult levels within 2 days of NH4Cl treatment.
- Actinomycin D inhibited both the increase in PDG activity and ammonia excretion, suggesting a role for gene expression.
Conclusions:
- Renal phosphate-dependent glutaminase (PDG) plays a direct and critical role in the adaptation of ammonia excretion to acidosis in infant rats.
- Unlike adult rats, the adaptive response in infant rats is highly dependent on enzyme synthesis, as indicated by actinomycin D's inhibitory effect.
- These findings highlight key differences in renal acid-base regulation between developing and adult mammals.
Abstract:
The purpose of this investigation was to determine the role of enzyme adaptation in the response of ammonia excretion to acidosis in developing rats. The response of renal ammonia excretion was low in infant rats (7-12 days old) following administration of a single dose of acidifying salt (5 mmol NH4CL/kg). However, repeated administration (2 times daily) of the salt increased ammonia excretion two- to threefold within 2 days. This adaptive response was associated with a concomitant rise in renal phosphate-dependent glutaminase (PDG) activity; PDG activity increased from approximately 36% adult level in untreated infants to 79% adult level in infants given NH4Cl for 2 days. Ammonia excretion and PDG activity decreased in parallel following cessation of NH4Cl treatment. Administration of the antibiotic, actinomycin D (100 mug/kg, ip, 2 times daily for 2 days) completely inhibited the response of PDG to repeated NH4Cl administration. In contrast to the situation previously observed in adult rats, actinomycin D treatment prevented the acid-induced rise in renal ammonia excretion. These results suggest that the level of renal PDG plays a more direct role in the adaptation of ammonia excretion to acidosis in infant rats than in adults.