Effect of prostaglandin E2 on agonist-stimulated cAMP accumulation in the distal convoluted tubule isolated from the rabbit kidney.
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)
Griffiths
N M
NM
Laboratoire de Physiologie Cellulaire, URA 219 CNRS, Collège de France, Paris.
Brick-Ghannam
C
C
Siaume-Perez
S
S
Chabardès
D
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D010281:Parathyroid Hormone; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D014660:Vasoactive Intestinal Peptide; D002116:Calcitonin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015232:Dinoprostone; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine