Effect of Prostaglandin E2 on Agonist-Stimulated cAMP Accumulation in the Distal Convoluted Tubule Isolated From the Rabbit Kidney

Pflugers Arch. 1993 Mar;422(6):577-84. doi: 10.1007/BF00374005.

Abstract

The effects of calcitonin, vasoactive intestinal peptide (VIP), parathyroid hormone (PTH) and isoprenaline on intracellular cAMP accumulation were determined in the distal tubule (DCT) microdissected from collagenase-treated rabbit kidney. In DCTb (the initial "bright" portion) calcitonin (10 ng/ml) elicited a highly reproducible response 203.7 +/- 19.1 fmol cAMP mm-1 4 min-1 (SE,N = 13) whereas VIP-induced cAMP accumulation was less and more variable from one experiment to another (1 microM, 97.2 +/- 17.8 fmol mm-1 4 min-1, SE, N = 12). When used in combination, these two agonists were non-additive, indicating stimulation of a single pool of cAMP in DCTb. In DCTg, ("granular") which consists of at least two cell types, PTH (100 nM) elicited a marked, reproducible accumulation of cAMP (154.3 +/- 27.0 fmol mm-1 4 min-1; SE, N = 5). Isoprenaline (1 microM) and VIP (1 microM) induced much smaller increases in cAMP levels 20.9 +/- 2.7 and 29.4 +/- 4.1 fmol mm-1 4 min-1 (SE, N = 5) respectively, and, when used in combination, were non-additive, demonstrating that VIP and isoprenaline are active on the same cell type. In DCTb, prostaglandin E2 (PGE2) inhibited both calcitonin- and VIP-stimulated cAMP accumulation (calcitonin 57.8 +/- 2.7% inhibition, SE, N = 16; VIP, 80.6 +/- 2.1% inhibition, SE, N = 5). The EC50 values for calcitonin were 1.21 +/- 0.33 ng/ml and 1.83 +/- 0.25 ng/ml (SD, N = 3) in the absence and presence of PGE2 (300 nM) respectively with an IC50 for PGE2 of 26.3 +/- 6.3 nM (SE, N = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology
  • Animals
  • Calcitonin / pharmacology
  • Cyclic AMP / metabolism*
  • Dinoprostone / pharmacology*
  • Isoproterenol / pharmacology
  • Kidney Tubules, Distal / drug effects
  • Kidney Tubules, Distal / metabolism*
  • Male
  • Parathyroid Hormone / pharmacology
  • Rabbits
  • Vasoactive Intestinal Peptide / pharmacology

Substances

  • Parathyroid Hormone
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
  • Vasoactive Intestinal Peptide
  • Calcitonin
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Dinoprostone
  • Isoproterenol
  • 1-Methyl-3-isobutylxanthine