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Inhibitors of arachidonic acid metabolism modulate the insulin‐like growth factor‐1‐induced growth of proximal tubular cells in primary culture
Author(s) -
GEKLE Michael,
POLLOCK Carol A
Publication year - 1997
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1997.tb00215.x
Subject(s) - nordihydroguaiaretic acid , arachidonic acid , epoxygenase , endocrinology , medicine , phospholipase a2 , growth factor , lipoxygenase , cyclooxygenase , biology , biochemistry , enzyme , receptor
Summary: Insulin‐like growth factor 1 (IGF‐1) is involved in the regulation of kidney growth during maturation as well as during regenerative processes. Some observations point to eicosanoids as possible intracellular mediators. In rat proximal tubular cells in primary culture we found that IGF‐1 (100 ng/mL) stimulated the release of arachidonic acid. We therefore investigated the effects of different inhibitors of arachidonic acid handling on IGF‐1‐induced hypertrophy (increase in cell protein) and hyperplasia (increase in cellular thymidine incorporation and cell number). the hypertrophic response was abolished by dibucaine (inhibitor of phospholipase A 2 ) or proadifen (inhibitor of cytochrome P‐450 enzymes). Clotrimaole (inhibitor of epoxygenase) reduced the hypertrophic response significantly. Indomethacin (inhibitor of cyclooxygenase) or NDGA (nordihydroguaiaretic acid; inhibitor of lipoxygenase) did not affect IGF‐1‐ induced hypertrophy. the hyperplastic response was abolished completely in the presence of dibucaine, and reduced significantly in the presence of proadifen or clotrimazole. Indomethacin did not affect the hyperplastic response, whereas NDGA reduced it slightly under certain conditions. From our results we conclude that the action of IGF‐1 on growth of proximal tubular cells is, at least in part, mediated by arachidonic acid or its cytochrome P‐450 metabolites. the underlying mechanism of action might be either stimulated metabolism or enhanced release of arachidonic acid.