Biomedical Sciences ETDs

Publication Date

4-17-1978

Abstract

Thie purpose of these studies was to clarify the functional significance of glutamine penetration and metabolism in postnatal increas1e in renal a1T111onia production using rat kidney slices .

Glutamine uptake, metabolism and ammoniagenesis were studied in kidney slices isolated from mature, gonadectomized males and females, and newborn rats in the presence of varying concentrations of glutamine. Slices isolated from mature intact females showed significantly higher conversion of 14C-glutamine into 14co2 and NH3 without any change in total uptake compared to all other experimental groups. Ovariectomy reduced CO2 and NH3 production without any effect on glutamine uptake. In contrast, castration did not significantly affect CO and NH3 production. Oxygen consumption was not sex dependent, but gonadectomy in general reduced it. Newborn males and females (20-21 days old) showed no differences in glutamine uptake, CO and NH production. However, newborn rat kidney slices showed lower uptake, CO2 and NH3 production, and o2 consumption compared to adult kidney slices. Thus, even though sex hormones do not appear to regulate peritubular transport of glutamine into renal cells, glutamine metabolism and ammoniagenesis in female rats a1re under possible control of ovarian sex hormones.

Glutamine penetration, co2 and NH3 production in kidney slices isolated from nonacidotic and acidotic rats are dependent upon the pH and temperature of incubation. The optimal pH for maximum accumulation of glutamine in nonacidotic slices was 7.3 at 37°C and 7.5 at 25°C. The ratio of hydroxyl to hydrogen ion concentration (OH-/ H+ ratio) in the medium for maximal transport of glutamine remained constant at about 10 regardless of temperature. Transport and metabolism of glutamine increased in rats made acidotic. The optimum pH for transport and metabolism in acidotic slices was 6.6 at 37°C and 6.8 at 25°C. Evaluation of the data showed glutamine transport and its metabolism to CO2 are at their maximum at a fixed level of OH-/ H+ ratio of 0.4. Arrmonia production in nonacidotic and acidotic kidney slices increased as the pH of the medium was increased.

Developmental changes in glutamine penetration, CO2 and NH3 production were studied in kidney slices isolated from 12 and 18 day old rats. The ability to accumulate and metabolize glutamine was lower in the newborns than in the adults and increased with the age of the animal. Chronic acidosis increased glutamine uptake, CO2 and NH3 production significantly in both age groups. However, acute acidosis failed to show any significant changes compared to nontreated controls even though urine pH and blood pH were comparable to those of chronically acidotic group. The lower capacity of the newborn animals to accumulate and metabolize glutamine can only be explained due to ill-developed transport system(s) existing in their kidneys.

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Sidney Solomon

Second Committee Member

Stephen C. Wood

Third Committee Member

Illegible

Fourth Committee Member

William Raleigh Galey Jr.

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