Effects of chloropyramine, dimethindene and diphenhydramine on transepithelial ion transport: studies in bovine tracheal epithelium and frog skin.
The effects on transepithelial ion transports of chloropyramine, dimetindene and diphenhydramine, which are three antagonists of H1-receptors of histamine, were examined in bovine tracheal epithelium and in frog skin. The short-circuit current I0 across bovine tracheal epithelium is the sum of active secretion of Cl- and absorption of Na+. In this tissue, all three drugs induced a reversible, dose-related inhibition of I0, up to 100%. The concentrations giving 50% of maximal effect were 1.4 X 10(-4) M for chloropyramine, 2.0 X 10(-4) M for dimetindene and 2.5 X 10(-4) M for diphenhydramine. The effect was unrelated to the agonist binding site of H1-receptors of histamine, since it was not altered in the presence of 10(-3) M histamine. Experiments in which Na+ transport was selectively reduced by 5 X 10(-5) M amiloride, or in which Cl- transport was selectively abolished by 10(-3) M furosemide, 10(-4) M bumetanide or Cl- removal, indicated that Na+ and Cl- transports were equally affected by the drugs. The action of chloropyramine was composed of an early inhibition of Na+ and Cl- movements, followed by a slow recovery of Cl- secretion. In frog skin, each one of the three H1-antagonists modified the I0, following two main patterns of response, a stimulation at the lower concentrations tested, or an inhibition at higher concentrations. Dose-response relationships were obscured by a large variability in response of individual skins. These observations in bovine tracheal epithelium and frog skin suggest that H1-antagonists might alter the functioning of other epithelia as well.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002712:Chlorides / Q000378:metabolism*; D004115:Dimethindene / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005029:Ethylenediamines / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D011895:Rana ridibunda; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects*
D002712:Chlorides; D005029:Ethylenediamines; D006634:Histamine H1 Antagonists; C004664:chloropyramine; D004115:Dimethindene; D004155:Diphenhydramine; D012964:Sodium