PGE2 reverses AVP inhibition of HCO3- absorption in rat MTAL by activation of protein kinase C

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Abstract

In the medullary thick ascending limb (MTAL) of the rat, prostaglandin E2 (PGE2) reverses inhibition of HCO3- absorption (JHCO3) by arginine vasopressin (AVP) by inhibiting AVP-stimulated adenosine 3′, 5′-cyclic monophosphate (cAMP) production. To determine whether this regulation by PGE2 involves protein kinase C (PKC), MTAL segments were perfused in vitro with physiological solutions containing 25 mM HCO3- (pH 7.4). With 10-10 M AVP in the bath, addition of 10-6 M PGE2 to the bath increased JHCO3 from 7.8 ± 0.4 to 13.0 ± 1.1 pmol·min-1·mm-1 (P < 0.01). This effect was blocked completely by pretreatment with the PKC inhibitors staurosporine or chelerythrine chloride (10-7 M in the bath). With both AVP and PGE2 in the bath, addition of staurosporine or chelerythrine to the bath decreased JHCO3 from 12.2 ± 1.1 to 7.3 ± 0.6 pmol·min-1·mm-1 (P < 0.005). Neither staurosporine nor chelerythrine affected JHCO3 under basal conditions or in the presence of AVP alone. With AVP in the bath, addition of phorbol 12-myristate 13-acetate (PMA, 10-6 M) to the bath increased JHCO3 from 5.0 ± 0.5 to 9.1 ± 1.0 pmol·min-1·mm-1 (P < 0.01). Similar to PGE2, PMA had no effect on JHCO3 in the absence of AVP or in the presence of 10-6 M bath forskolin. The effect of PMA to stimulate JHCO3 in the presence of AVP was abolished by pretreatment with pertussis toxin (2 × 10-11 M). We conclude that 1) PGE2 reverses AVP inhibition of HCO3- absorption by activation of PKC, 2) PKC likely increases JHCO3 by inhibiting AVP-stimulated cAMP production via a Gi-dependent mechanism, and 3) PKC activity has no influence on basal HCO3- absorption rate. adenosine 3′, 5′-cyclic monophosphate; signal transduction; phorbol ester;.

Original languageEnglish (US)
Pages (from-to)F978-F985
JournalAmerican Journal of Physiology
Volume270
Issue number6 PART 2
DOIs
StatePublished - Jan 1 1996

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Keywords

  • Inhibitory g protein
  • Prostaglandin e receptor

ASJC Scopus subject areas

  • Physiology (medical)

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