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)
JournalAmerican Journal of Physiology
Volume270
Issue number6 PART 2
StatePublished - 1996

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Arginine Vasopressin
Dinoprostone
Protein Kinase C
Baths
Extremities
Staurosporine
Adenosine
Protein C Inhibitor
Pertussis Toxin
Phorbol Esters
Colforsin
Protein Kinase Inhibitors
Signal Transduction
Acetates

Keywords

  • Inhibitory g protein
  • Prostaglandin e receptor

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

PGE2 reverses AVP inhibition of HCO3 - absorption in rat MTAL by activation of protein kinase C. / Good, David.

In: American Journal of Physiology, Vol. 270, No. 6 PART 2, 1996.

Research output: Contribution to journalArticle

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title = "PGE2 reverses AVP inhibition of HCO3 - absorption in rat MTAL by activation of protein kinase C",
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;.",
keywords = "Inhibitory g protein, Prostaglandin e receptor",
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T1 - PGE2 reverses AVP inhibition of HCO3 - absorption in rat MTAL by activation of protein kinase C

AU - Good, David

PY - 1996

Y1 - 1996

N2 - 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;.

AB - 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;.

KW - Inhibitory g protein

KW - Prostaglandin e receptor

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M3 - Article

VL - 270

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

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