Effect of aging on the mechanisms of PTH-induced calcium influx in rat intestinal cells

✍ Scribed by Virginia Massheimer; Gabriela Picotto; Ricardo Boland; Ana R. De Boland

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 206 KB
• Volume: 182
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(200003)182:3<429::aid-jcp14>3.0.co;2-s

✦ Synopsis

We have investigated the effects of aging on parathyroid hormone (PTH) modulation of intracellular calcium homeostasis and their relationship to signal transduction pathways in isolated rat duodenal cells (enterocytes). PTH (10 Ϫ8 -10 Ϫ9 M) increased enterocyte 45 Ca 2ϩ influx and intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) to a greater extent (twofold and 50%, respectively) in aged (24 months) than in young (3 months) animals. The [Ca 2ϩ ] i response of old cells to the hormone was slower, lacking the early phase of changes in cytosolic Ca 2ϩ . Ca 2ϩ influx induced by PTH was prevented by the protein kinase A antagonist Rp-cAMPS in both young and aged enterocytes, whereas neomycin and compound U73122, inhibitors of PLC-catalyzed phosphoinositide hydrolysis, abolished hormone-dependent Ca 2ϩ influx in young but had no effect on aged cells. Higher basal adenylyl cyclase (AC) activity and cAMP content were detected in old enterocytes. PTH increased the absolute levels of cAMP in aged cells and AC activity of microsomes isolated therefrom to a greater extent (Ն twofold) than in young enterocytes/membranes. In young cells, the hormone also induced a rapid and transient release of inositoltrisphosphate (IP 3 ) and diacylglycerol (neomycinsensitive) at 45 sec, and a delayed phase of DAG at 5 min (neomycin-insensitive). The early formation of IP 3 and DAG was blunted in aged animals. These results suggest that both the PLC and adenylyl cyclase cascades are involved in PTH stimulation of Ca 2ϩ influx in duodenal cells. During aging, however, only the cAMP pathway is operative, mediating a potentiation of the effects of the hormone. Additional studies are required to establish the relative role of PTHdependent messenger systems in the regulation of intestinal calcium absorption and age-related abnormalities.