Regulation of HCO3- absorption by prostaglandin E2 and G proteins in rat medullary thick ascending limb.
Arginine 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 JHCO3 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) MAVP 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 JHCO3 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 pertusis toxin (PTX, 2 x 10(-11) or 10(-8) M). Neither CTX nor PTX affected inhibition of JHCO3 by hyperosmolality. These results demonstrate that PGE2 reverses inhibition of JHCO3 by AVP by acting via a PTX-sensitive G protein (presumably Gi) 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.
Good
D W
DW
Department of Medicine, University of Texas Medical Branch, Galveston 77555, USA.
George
T
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D000042:Absorption; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D007679:Kidney Medulla; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001639:Bicarbonates; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D005576:Colforsin; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D015232:Dinoprostone