Age-related change in parathyroid hormone-dependent cyclic AMP formation in rat kidney

Marcus, Robert; Gonzales, David A.

doi:10.1016/0047-6374(82)90102-6

Cited by 11 publications

(2 citation statements)

References 17 publications

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“…The decline in the PTH response with age may be due to the increased circulating levels of PTH, perhaps as a consequence of reduced renal clearance of PTH (38, 39), which may lead to downregulation of renal PTH receptors. Marcus and Gonzales reported that PTH-stimulated CAMP production is attenuated in cortical renal slices from 12-month-old rats compared to slices from 2-month-old rats (40), whereas Armbrecht et al demonstrated a decline in the PTH-induced 1 ,25-(OH),D3 synthesis in 13-month-old rats compared to 2-month-old rats (41). These findings suggest that the aged kidney may possess a degree of end-organ insensitivity toward the phosphaturic and vitamin D,-stimulating effects of PTH.…”

Section: Discussionmentioning

confidence: 96%

Changes in Renal Phosphate Reabsorption in the Aged Rat

Mulroney

Woda

Haramati

1998

Experimental Biology and Medicine

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Depletion of inorganic phosphate (Pi) reserves occurs frequently in aged animals and can result in diminished bone mineralization and osteoporosis. This altered Pi balance results from a reduction in intestinal Pi absorption and an elevation in renal Pi excretion. Since the kidney plays a central role in maintaining Pi homeostasis, we tested whether the increased phosphaturia seen with aging is a consequence of changes in the intrinsic tubular capacity to reabsorb Pi (TmPi). Male Wistar rats (12-, 18-, and 24-months-old) were acutely thyroparathyroidectomized (TPTX) and prepared for renal clearance studies in the presence and absence of fixed levels of parathyroid hormone (synthetic PTH-(1-34), 1 U/kg/min). The maximum capacity for Pi transport (TmPi) was assessed by infusion of Pi at progressively higher rates (0-6 micromol/min) to increase the filtered load of Pi and facilitate the determination of the TmPi. TmPi declined significantly with age (3.51 +/- 0.12 vs 3.04 +/- 0.19 vs 2.30 +/- 0.18 micromol/ml, for 12-, 18-, and 24-month-old rats, respectively, P < 0.05) in TPTX rats. Administration of PTH markedly reduced the TmPi in all age groups. Although the TmPi attained was similar among the age groups (1.15 +/- 0.13 vs 1.15 +/- 0.06 vs 1.03 +/- 0.09 micromol/ml, for 12-, 18-, and 24-month-old rats, respectively), the magnitude of the reduction in the presence of PTH declined from 67% in 12-month-old rats to 62% and 55% in 18- and 24-month-old rats, respectively. These results demonstrate that aging is associated with a PTH-independent decrease in the intrinsic capacity of the kidney to reabsorb phosphate. Further, the kidney of the aged rat can respond to a pharmacological dose of PTH with appropriate reductions in the TmPi although the magnitude of the response declines with age.

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Section: Discussionmentioning

confidence: 96%

Changes in Renal Phosphate Reabsorption in the Aged Rat

Mulroney

Woda

Haramati

1998

Experimental Biology and Medicine

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“…Increased level of immunoactive PTH was reported in the senescent rat (13). However, accumulation of cAMP in response to PTH was found to be decreased in renal slices from 12-month-old rats in comparison to 2-month-old rats (14). We examined the effect of age on renal cell 45Ca2+ efflux and the responsiveness of the system to PTH.…”

Section: Introductionmentioning

confidence: 99%

Regulation of renal sodium calcium exchange by PTH: alteration with age.

Liang

Hanai

Ishida

et al. 1990

Environ Health Perspect

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Parathyroid hormone, when incubated with renal cells acting in vivo and in vitro, increased Na+/ Ca2" exchange activity. The effect of parathyroid hormone was specific for biologically active analogs and could be mimicked by cAMP and forskolin. Parathyroid hormone-sensitive Na+/Ca2+ exchange activity was markedly blunted in cells from senescent rats. Parathyroid hormone-stimulated adenylate cyclase was also decreased in aging. In contrast, forskolin-stimulated Na+-dependent Ca"+ efflux and adenylate cyclase did not change with senescence. Decrease of PTH binding sites was observed in cells from old rats. Further, cells from 24-month-old rats had decreased Gs and Gi proteins, as detected by ADP-ribosylation. Since serum iPTH level was elevated in the old rat and could contribute to the desensitization to PTH, we tested this hypothesis by comparing sham-operated and PTX animals. The decreases in PTH-sensitive Nae/Ca2' exchange activity and adenylate cyclase activity in cells from 24-month-old rats could be completely negated by parathyroidectomy. Decrease in PTH binding sites and contents of Gs and Gi in cells from aged-rats was partially negated by the surgery. In conclusion, our results suggested that the age related blunting in responses of renal cells to PTH was due, at least in part, to the elevated serum iPTH level in old rats.

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