Arachidonic acid metabolism and regulation of ion transport in rabbit Clara cells

Abstract

Sonicates of freshly isolated Clara cells produced thromboxane B2 (TxB2), prostaglandin (PG) D2, PGE2, PGF2 alpha, hydroxyheptadecatrienoic acid (HHT), and 12-hydroxyeicosatetraenoic acid (12-HETE) as detected using high-performance liquid chromatography (HPLC). Sonicates of Clara cells cultured on collagen matrices produced the same metabolites. Rates of [3H]arachidonic acid metabolism increased in culture, but the changes were not associated with changes in cell number. Sonicates of freshly isolated tracheal cells produced mainly 12-HETE. Cyclooxygenase products were not produced consistently. Sonicates of tracheal cultures produced significant quantities of TxB2, PGD2, PGE2, PGF2 alpha, and HHT, but 12-HETE remained the major metabolite. Equivalent short-circuit current (Ieq) across cultured Clara cell epithelia was unaffected by bilateral exposure to TxB2, PGD2, PGE2, PGF2 alpha, HHT, or 12-HETE. A minor (1%) decrease in transepithelial resistance (Rt) followed exposure to PGD2. Indomethacin had no significant effect on Rt or Ieq, but exposure of indomethacin-pretreated preparations to PGE2 revealed a minor (2%) increase in Ieq. In contrast, tracheal cell epithelia exhibited significant changes in Rt and Ieq in response to PGF2 alpha, PGE2, and HHT. These results indicate that Clara cells metabolize arachidonic acid to biologically active eicosanoids, but the resulting products do not play a major role in regulation of transepithelial ion transport by this cell type.