Prostaglandin E2 production in rat IMCD cells. II. Possible role for locally formed dopamine.
Dopamine has been proposed as an intrarenal natriuretic hormone. We reported previously that inner medullary collecting duct (IMCD) cells express a novel DA2-like dopamine receptor (namely, DA2K) that is linked to stimulation of prostaglandin E2 (PGE2) production. In this study we examined whether locally formed dopamine could stimulate PGE2 production in cultured IMCD cells. L-Dopa stimulated PGE2 production dose dependently in cultured IMCD cells (concentration for half-maximal stimulation, 54.3 microM; maximal stimulation, 212.7% of basal), with the maximal stimulation similar to that obtained with dopamine. This effect was blocked by aromatic L-amino acid decarboxylase (AADC) inhibitors and DA2-receptor antagonists. IMCD cells also had measurable AADC activity and produced dopamine from exogenously added L-dopa. AADC inhibitors and DA2 antagonists also lowered basal PGE2 levels, suggesting that dopamine was being formed constitutively in culture. These results suggest that cultured IMCD cells have the capacity to take up and convert L-dopa to dopamine, which then stimulates PGE2 production via DA2K receptors. These results further suggest that locally formed dopamine could act as an autocrine/paracrine hormone in the kidney inner medulla to regulate PGE2 synthesis and water and electrolyte excretion.
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York 10029.
T L
TL
Huo
A
A
Grenader
P
P
Blandina
D P
DP
Healy
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D018492:Dopamine Antagonists; D006834:Hydrazines; D007980:Levodopa; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D015232:Dinoprostone; D002230:Carbidopa; D004298:Dopamine