Prostaglandin release mediates drug-induced stimulation of sodium transport in frog skin: the effects of quinacrine.
Quinacrine markedly increased the release of prostaglandin E2 (PGE2) into the basolateral solution of the bullfrog skin from a control value of 32.7 +/- 21.7 pg per 20 min period to a stimulated value of 8593.1 +/- 4112.3 pg per 20 min period. Quinacrine increased the amiloride-sensitive short circuit current from 20.7 +/- 2.1 microA cm-2 to 45.4 +/- 6.5 microA cm-2. The stimulatory effects of quinacrine on both short circuit current and prostaglandin release were blocked in skins pretreated with indomethacin (10(-6) M). Quinacrine did not block either the stimulation of the short circuit current or the increase in PGE2 release caused by the calcium ionophore, ionomycin. These results suggest: (a) the release of PGE2 and the stimulation of the short circuit current caused by quinacrine are linked since blocking PGE2 release inhibits the stimulation of the short circuit current; (b) given the complexity of its actions, quinacrine is a poor tool to examine whether the effects of a given agent are mediated through the activation of endogenous phospholipases. In addition our results taken together with other findings in the literature suggest that there is a diverse group of compounds that stimulate transepithelial sodium transport by releasing PGE2.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D015232:Dinoprostone; D004987:Ethers / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D015759:Ionomycin; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D011892:Rana catesbeiana; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D004987:Ethers; D011453:Prostaglandins; D011458:Prostaglandins E; D015759:Ionomycin; D000584:Amiloride; D012964:Sodium; D011796:Quinacrine; D015232:Dinoprostone; D007213:Indomethacin