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The role of Ca2+ in the in situ secretory response of rat colon and pig ileum was studied by chelation depletion of Ca2+ and by treatment with chlorpromazine. The effect of depleting lumenal Ca2+ by chelation and the effect of intraperitoneal administration of chlorpromazine were determined relative to colonic permeability and net fluid flux measured across the rat colon or pig ileum. Replacement of Ca2+ in the perfusate by 1.0 mM ethyleneglycol-(bis-beta-ethylaminoether) (EGTA) did not produce significant changes in the net absorptive fluid flux measured in the control state or in the net secretory fluid flux caused by secretory detergent agents. The concentration of EGTA used in the perfusate did not alter mucosal permeability. Nonsecretory bile acids or A23187 had no effect on net colonic fluid flux or on colonic permeability to mannitol in the rat. The known correlation between net fluid flux and increased colonic permeability to polar molecules has been confirmed for the secretory detergent compounds. Chlorpromazine pretreatment caused a partial reversal of net secretory fluid fluxes induced by deoxycholate and high concentrations (6.0 mM) of ricinolate and dioctyl sulfosuccinate without significantly altering mucosal permeability to mannitol. We conclude that depletion of lumenal Ca2+ is not an effective method for determining the possible Ca2+ dependence of these intestinal secretory events. The antisecretory actions of chlorpromazine may provide some indirect evidence for Ca2+ involvement in the secretory effects of the detergent class of laxative compounds. Permeability may be essential for secretion caused by these agents, but the driving force would appear to be provided by the active transfer of electrolytes from the blood to the lumen of the colon.

The association between reported intestinal fluid secretory activity of bile acids and Ca2+ ionophore properties was investigated in a pig jejunal brush border vesicle system. Secretory and nonsecretory bile acids and hydroxy-fatty acids were tested to see if Ca2+ ionophore activity is a general property of all bile acids and hydroxy-fatty acids, or if it is confined to compounds with recognized fluid secretory activity. Ionophore activity was attributed to compounds which could increase rates of Ca2+ influx and efflux from brush border vesicles under conditions where nonspecific permeability to sorbitol was not affected. The recognized secretory agents chenodeoxycholate and dioctyl sulfosuccinate had Ca2+ ionophore activity in the test system. The nonsecretory agents cholate, hyodeoxycholate and 4-hydroxybutyrate had no detectable activity, while ursodeoxycholate showed minor ionophore activity. Due to complications resulting from Ca2+ sequestration it was impossible to determine the Ca2+ ionophore activity of 12-hydroxystearate in this system. The detergent properties of all these agents are known to increase intestinal permeability, but detergent strength, as measured by concentration required to increase mannitol exchange across vesicle membranes, did not correlate well with secretory activity. We conclude that intestinal fluid secretion caused by bile acids and hydroxy-fatty acids could be controlled partially by Ca2+ ion interactions which could include intracellular signal effects of Ca2+ on anion permeability of the brush border membrane as well as possible increases in permeability of the tight junctions, and local hypertensive effects.

Cynomolgus monkeys (Macaca fascicularis) were fed diets containing 25% rapeseed oil (RSO), partially-hydrogenated herring oil (PHHO) or a 3:1 mixture of lard/corn oil as control (CON) for 4 months. The RSO contained approximately 25% of the fatty acids as erucic acid (cis-docos-13-enoic, 22:1w9) while the PHHO contained a similar concentration of mainly cetoleic acid (cis-docos-11-enoic, 22:1w11). The CON contained no 22:1 acids. The monkeys developed the expected myocardial lipidosis, somewhat more pronounced in the RSO than the PHHO group, but small foci of mononuclear cell infiltration, while infrequent, occurred in all three groups. Significant intergroup differences in biochemical or hematologic measurements of serum constituents were an increase in serum cholesterol concentration in the RSO group and an increase in serum glutamicoxaloacetic transaminase activity in both RSO and PHHO groups at certain intervals. The shorter proportion of M. fascicularis life span represented by this experiment may account for the absence of clear intergroup differences such as are reported in rats used in similar studies.