Calcitonin inhibits proton extrusion in resorbing rat osteoclasts via protein kinase A

Hiroshi Kajiya, Fujio Okamoto, Hidefumi Fukushima, Koji Okabe

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H+ transport. In this study, we examined the effects of calcitonin on H+ extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2′7′-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H+ extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H+-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A1- sensitive and an amiloride-sensitive system [H+ extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na+/H+ exchanger (NHE), respectively]. Calcitonin inhibited both H+ extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H+ extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H+ transport by calcitonin are important for the regulation of bone resorption.

Original languageEnglish
Pages (from-to)651-658
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume445
Issue number6
DOIs
Publication statusPublished - 2003 Mar 1

Keywords

  • Bone resorption
  • Calcitonin
  • Intracellular pH
  • Osteoclasts
  • Proton extrusion

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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