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Cholecystokinin (CCK) receptors are currently divided into at least two subtypes: a CCK-A subtype, responsive to the sulfated form of cholecystokinin octapeptide (CCK-8) and selectively antagonized by L-364,718, and a CCK-B subtype, which shares equal affinities for gastrin and CCK-8. In the present study the receptor subtype that mediates guinea pig ileal secretion by evaluating the potencies of CCK- and gastrin-related peptides to evoke increases in transmucosal short-circuit current was characterized. The antagonist potencies of L-365,260 (CCK-B selective) and L-364,718 (CCK-A selective) against CCK-8 were also determined. Both CCK-8 and cerulein, when added to the serosal side of the tissue, evoked increases in the short-circuit current, having EC50 values of 0.8 and 0.2 nmol/L, respectively. Desulfated (SO3) CCK-8, CCK-4, gastrin17-I, pentagastrin, gastrin17-II, and gastrin13-I were relatively weak agonists (EC50 greater than 1000 nmol/L. Cholecystokinin octapeptide-induced short-current responses were competitively antagonized by L-364,718 (pA2, 10.3) and L-365,260 (pA2, 7.4). The high selectivity of the tissue for sulfated CCK-8 suggests that the secretory effect of CCK-8 on guinea pig ileal electrolyte transport is mediated by a CCK-A receptor. The potent effect of L-364,718 against CCK-8 is also consistent with an action at the A-subtype receptor.

The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and dihydroxy bile salts (deoxycholate, chenodeoxycholate, and taurodeoxycholate), whereas no activity was seen with trihydroxy (cholate, glycocholate, and taurocholate) and tri-keto (dehydrocholate) bile salts. The relative effects on water transport were paralleled by their abilities to lyse the erythrocyte, a membrane model. These two biological effects were related to the surface properties of the agents, as determined by critical micelle concentration and surface tension reduction. We further characterized the action of deoxycholate on hamster small intestine, in vivo. Net water secretion was accompanied by increases in permeability of the mucosa to inulin, dextran, and albumin. These secretory and permeability changes were accompanied by both biochemical and histological alterations: exfoliation (DNA release), membrane effects (sucrase release), and shortened villi. Electron microscopy revealed extensive alteration of the brush border membrane with a decrease in binding of lanthanum and the development of permeability to tracer in villus tip cells. In contrast, taurocholate, which did not alter water transport, did not affect intestinal permeability or the brush border membrane. We believe that the surface properties of anionic surfactants cause changes in absorptive cell membranes which result in intestinal secretion.