title: Mediators of the secretory response to kinins.
abstract: The output of immunoreactive (i) 6 keto prostaglandin F1 alpha (i6ketoPGF1 alpha), iPGE2 and ithromboxane B2 (iTXB2) from isolated colonic epithelium of the rat into the apical and basolateral bathing solution has been measured. In some instances tissues were also voltage clamped at 0 mV to measure short circuit current (SCC). Kallidin (lysylbradykinin) stimulated the output of all three eicosanoids, specifically from the basolateral face of the tissue. The output was similar whether or not the tissues were short circuited. Both the SCC response and eicosanoid output were dependent upon the concentration of kallidin, but not in a strictly proportional manner, there being relatively more eicosanoid output at submaximal kinin concentrations. Indomethacin, 5 microM, abolished the eicosanoid output, in response to kinin, while some part of the SCC response remained. Calcium removal from the basolateral bathing fluid severely attenuated the SCC response, reduced the output of i6ketoPGF1 alpha to half, but left the output of iPGE2 unchanged. In the presence or absence of calcium it is probable that sufficient PGE material is released to cause part of the SCC changes seen with kinin. Kinin and PGE1 increased the cyclic AMP content of intact epithelia, provided a phosphodiesterase inhibitor was added at the same time. It is proposed that kinin causes an increase in calcium influx at the basolateral pole of the tissue. This calcium is necessary for the production of some eicosanoids and the subsequent generation of cyclic AMP, which then increases apical chloride permeability. In addition, calcium may facilitate entry of chloride through the basolateral face of the cells by activating a cotransport mechanism.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone; D004789:Enzyme Activation / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007609:Kallidin / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D011458:Prostaglandins E; D007609:Kallidin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin