Benzoquinolines and chloride secretion in murine colonic epithelium

1 In all, 27 compounds related chemically to phenanthrolines were investigated for their ability to stimulate electrogenic chloride secretion in murine colonic epithelia under short circuit current conditions. A total of 11 compounds, not previously examined, were shown to have substantial activity. Cumulative concentration - response relations were obtained in the presence of amiloride to inhibit electrogenic sodium absorption and Ba2+ to prevent potassium secretion. 2 Single- or double-ring substitutions in 1,10 phenanthroline (EC50 = 612 muM) produced only modest increases in affinity of between 0.7- and 2.1-fold. 3 Naphthalenes with either one or two ring nitrogens showed some activity but had very low affinity, et some (e.g. isoquinoline. EC50 = 700 muM) were able to produce maximal responses. 4 Removal of one nitrogen from 1,10-phenanthroline or from 4,7-phenanthroline gave, respectively, 7,8-benzoquinoline and 5,6-benzoquinoline, These two were the most active compounds found, the EC50 for 5,6-benzoquinoline being 29 muM. 5 Most concentration - response curves were steep with Hill slopes of approximately 3. At high concentration. some compounds inhibited the response, producing a characteristic bell shape. 6 5,6- and 7.8-benzoquinoline may be useful starting points for the synthesis of more potent agents by the addition of ring substituents.