Role of prostaglandin release in the response of tight epithelia to Ca2+ ionophores.
We have studied the effects of the Ca2+ ionophores A23187 and ionomycin on ion transport across amphibian skin and urinary bladder. Both A23187 and ionomycin stimulated transepithelial Na+ transport across the skin. Ionomycin also markedly increased the conductance of an amiloride-insensitive pathway. Both ionophores markedly stimulated the release of prostaglandin E2 (PGE2) into the solution bathing the serosal surface of the skin. Addition of indomethacin to the serosal bathing solution of the skin blocked both the stimulation of short-circuit current (Isc) and the release of prostaglandin caused by the ionophores. Acetylsalicylic acid also blocked the ionomycin-induced stimulation of Isc. These results suggest that the stimulation of Na+ transport caused by Ca2+ ionophores is mediated by the release of a product of the cyclooxygenase pathway, very likely PGE2. Ca2+ ionophores also stimulated the release of PGE2 in urinary bladders; however, they generally depressed Isc. Since the effect on Isc caused by the addition of exogenous PGE2 was different in urinary bladders than in skins, we suggest that at least part of the difference in the action of ionophores is due to the difference in the sensitivity of these epithelia to PGE2. Our results suggest that the heterogeneity of effects that Ca2+ ionophores cause in the physiological parameters of tight epithelia are not always the direct result of increased cytoplasmic Ca2+ but that they may be mediated by other tissue responses triggered by the addition of the ionophores.
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D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001693:Biological Transport, Active; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D015232:Dinoprostone; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D015759:Ionomycin; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011892:Rana catesbeiana; D011894:Rana pipiens; D012867:Skin / Q000166:cytology* / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology* / Q000187:drug effects
D002712:Chlorides; D004987:Ethers; D011453:Prostaglandins; D011458:Prostaglandins E; D000001:Calcimycin; D015759:Ionomycin; D012964:Sodium; D015232:Dinoprostone; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin