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Second messenger signaling in the regulation of cytosolic pH and DNA synthesis by parathyroid hormone (PTH) and PTH‐related peptide in osteoblastic osteosarcoma cells: Role of Na + /H + exchange
Author(s) -
Sugimoto Toshitsugu,
Kano Junichi,
Fukase Masaaki,
Fujita Takuo
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520105
Subject(s) - ionomycin , parathyroid hormone , cytosol , amiloride , chemistry , medicine , endocrinology , protein kinase c , calcium , signal transduction , protein kinase a , ionophore , second messenger system , dna synthesis , kinase , biology , biochemistry , enzyme , dna , sodium , organic chemistry
The present study was performed to investigate the regulation of cytosolic pH (pHi) and DNA synthesis by parathyroid hormone(PTH) and PTH‐related peptide (PTHrP) in osteoblasts, using osteoblastic osteosarcoma cells, UMR‐106 which possessed PTH‐responsive dual signal transduction systems (cAMP‐dependent protein kinase (PKA) and calcium/protein kinase C [Ca/PKC]) and amilorideinhibitable Na + /H + exchange system. Both human (h)PTH‐(1–34) and hPTHrP‐(1–34) caused a progressive decrease in pHi and the inhibition of [ 3 H]thymidine incorporation (TdR) to the same degree in a dose‐dependent manner with a minimal effective dose of 10 −10 M. Dibutyryl cAMP (10 −4 M) and Sp‐cAMPS (10 −4 M), a direct stimulator of PKA also caused a progressive decrease in pHi, and calcium ionophores (A23187 and ionomycin, 10 −6 M) caused a transient decrease in pHi. Pretreatment with amiloride (0.3 mM) mostly blocked dbcAMP‐and Sp‐cAMPS‐induced decrease in pHi but did not affect calcium ionophore‐induced decrease in pHi. In the presence of amiloride, PTH and PTHrP caused a transient decrease in pHi, which was similar to the pattern of calcium ionophore‐induced change in pHi. Amiloride did not affect the inhibition of TdR by PTH or PTHrP as well as that by cAMP analogues or calcium ionophores. The present study indicated that PTH and PTHrP caused cytosolic acidification through PKA‐inhibited Na + /H + exchange and increased cytosolic calcium‐induced pathway and that the regulation of DNA synthesis by PTH and PTHrP was not via Na + /H + exchange system. © 1992 Wiley‐Liss, Inc.