Regulation of HCO3- absorption by prostaglandin E2 and G proteins in rat medullary thick ascending limb

David W. Good, Thampi George

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Abstract

-Areinine vasopressin (AVP) inhibits HCO3- absorption (JHCO3 ) in the medullary thick ascending limb (MTAL) of the rat by increasing adenosine 3′,5′-cyclic monophosphate. Hyperosmolality also inhibits e/HCO3 via a pathway additive to inhibition by AVP. To determine whether these regulatory effects are modulated by prostaglandin E2 (PGE2), MTAL were isolated and perfused in vitro with 25 mM HCO3- solutions (pH 7.4; 290 mosmol/kgH2O). PGE2 10-6 M in the bath) had no effect on JHCO3 in the absence of AVP. In contrast, with 10-10 M AVP in the bath solution, addition of 10-8 or 10-6 M PGE2 to the bath increased JHCO3 from 9.7 ± 0.8 to 14.3 ± 1.1 pmol-min-1-mm-1 (P < 0.001). In the presence of AVP and hyperosmolality (75 mM NaCl added to perfusate and bath), PGE2 increased JHCO3 from 1.4 ± 0.1 to 7.5 ± 0.5 pmol-min-1. mm-1 (P < 0.005). PGE2 also stimulated JHCO. in the presence of AVP and hypertonic urea. Cholera toxin (CTX, 10-12-10-9 M in the bath) inhibited JHCo3 by 40%, and this inhibition was reversed by PGE2. PGE2 did not reverse inhibition of JHCO3 by forskolin. The stimulation of JHCO3 by PGE2 in the presence of AVP was blocked by pretreatment with pertussis toxin (PTX, 2 × 10-11 or 10-8 M). Neither CTX nor PTX affected inhibition of JHCO3 by hyperosmolality. These results demonstrate that PGE2 reverses inhibition of JHCO, by AVP by acting via a PTX-sensitive G protein (presumably G;) to inhibit AVP-stimulated adenosine 3′,5′-cyclic monophosphate production. PGE2 may act as a counterregulatory factor to maintain a stable rate of HCO3- absorption in the MTAL during antidiuresis when circulating AVP levels and medullary osmolality are elevated. vasopressin; adenosine 3′,5′-cyclic monophosphate; hyperosmolality; acid-base regulation; pertussis toxin

Original languageEnglish (US)
Pages (from-to)F711-F717
JournalAmerican Journal of Physiology
Volume270
Issue number5 PART 2
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Physiology (medical)

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