Effect of U-73,122, an inhibitor of phospholipase C, on actions of parathyroid hormone in opossum kidney cells

K. J. Martin, C. L. McConkey, A. K. Jacob, E. A. Gonzalez, M. Khan, J. J. Baldassare

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The relative roles of the adenylate cyclase-protein kinase A system (AC- PKA), the phospholipase C-protein kinase C system (PLC-PKC), and increases in cytosolic calcium in mediating the final actions of parathyroid hormone (PTH) remain ill defined. Although an important role for the PLC-PKC system in the regulation of phosphate transport in response to PTH has been suggested, previous studies from our laboratory and others, in OK cells, have emphasized the major role of AC-PKA. The present studies were designed to dissociate the second messengers for PTH by using an inhibitor of PLC (U-73,122). Studies were performed in confluent cultures of OK cells with and without preincubation with U-73,122 (1 μM). This inhibitor did not alter adenosine 3',5'-cyclic monophosphate (cAMP) production or the activation of PKA in response to PTH. Preincubation with U-73,122, however, totally abolished PTH- stimulated increases in diglyceride mass, consistent with inhibition of PLC. Activation of particulate PKC was then examined in response to PTH in the absence and presence of U-73,122. Although PTH resulted in an increase in particulate PKC activity in control cultures, this effect was abolished in the presence of U-73,122 and actually decreased significantly. Therefore, having documented marked attenuation of PLC-PKC, we next examined the effects of PTH on phosphate transport. Basal phosphate uptake was not altered by 1 μM U-73,122. Dose-response curves of the inhibition of phosphate transport in response to PTH were identical in the presence or absence of U-73,122. Thus inhibition of PLC and PKC activities did not alter the effects of PTH on phosphate transport. These data suggest that PLC-PKC may not be essential for the regulation of phosphate transport by PTH in OK cells and emphasize the major role of the PKA system in the regulation of this action of PTH.

Original languageEnglish (US)
Pages (from-to)F254-F258
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume266
Issue number2 35-2
DOIs
StatePublished - 1994

Keywords

  • phosphate
  • protein kinase C
  • second messengers
  • signal transduction

ASJC Scopus subject areas

  • Physiology

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