title: Effect of prostaglandin E2 on agonist-stimulated cAMP accumulation in the distal convoluted tubule isolated from the rabbit kidney.
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)
authors.affiliation: Laboratoire de Physiologie Cellulaire, URA 219 CNRS, Collège de France, Paris.
authors.forename: N M
authors.initials: NM
authors.lastname: Griffiths
authors.forename: C
authors.initials: C
authors.lastname: Brick-Ghannam
authors.forename: S
authors.initials: S
authors.lastname: Siaume-Perez
authors.forename: D
authors.initials: D
authors.lastname: Chabardès
mesh_terms: 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
chemical_list: 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