Parathyroid Hormone Stimulates the Mitogen-activated Protein Kinase Pathway of Intestinal Cells in Rats, a Mechanism Affected by Aging

GENTILI CLAUDIA; BOLAND, RICARDO; DE BOLAND A.

Buenos Aires

Congreso; V Congreso de la Sociedad Iberoamericana de Osteologia y Metabolismo Mineral. XVII Reunión Anual de la AAOMM.; 2000

SIBOMM/AAOMM

Parathyroid hormone (PTH), an 84 amino acid peptide, together with calcitonin andvitamin D, is involved in systemic calcium homeostasis in mammals. In the presentstudy, we evaluated the involvement of PTH [rPTH(1-34)] in the phosphorylationand activation of the growth-related protein, mitogen-activated-protein (MAP)kinases (p42/p44 MAPK) in enterocytes isolated from young (3-month-old) andaged (24-month-old) rats. Immunochemical analyses with anti-MAPK antibody,which recognized the two phosphorylated isoforms of the enzyme (p42 and p44)Bone Vol. 29, No. 3 Abstracts 307September 2001:294–313revealed that PTH rapidly stimulates tyrosine phosphorylation of MAPK. Hormoneeffects on MAPK were evident within 30 sec, peaking at 1 min (by fourfold). PTHresponse was dose-dependent (10211 to 1027 mol/L), with maximal stimulationachieved at 1029 to 1028 mol/L. PTH-induced MAPK phosphorylation waseffectively suppressed by the tyrosine-kinase inhibitors, genistein (100 mmol/L) andherbimycin (2 mmol/L). Moreover, the tyrosine phosphorylation and activation ofMAPK was dependent on Src kinase, because PP1 (10 and 20 mm), a specific Srcfamily tyrosine-kinase inhibitor, blocked PTH action. With aging, the response toPTH was significantly reduced. However, the amount of basal protein expressiondetermined by western blot analysis for MAPK was not different in the enterocytesfrom young and aged rats.The results obtained in this work expand our knowledge on the mechanism ofaction of PTH in duodenal cells, revealing that protein tyrosine phosphorylation islinked to PTH regulation of enterocyte MAPK activation, and that this mechanismis impaired with aging.