Search

Effects of glucagon (GN) on short-circuited mouse intestine were studied. GN (30 microgram . ml-1), added to the serosa of intestine mounted in an Ussing chamber and bathed in glucose-free Ringer, induced significant increases of 43% in serosal-to-mucosal Cl- flux (Js leads to m Cl), 315% in net Cl- secretion (Jnet Cl), 85% in net residual flux (J net R), 61% in short-circuit current (Isc), and 44% in open-circuit potential difference (PD). The mucosal-to-serosal Cl- flux and both unidirectional Na+ fluxes (Jm leads to s Na and Js leads to m Na) were unchanged. In a glucose Ringer bathing medium, GN exhibited no significant effects on ion fluxes and electrical parameters. To eliminate the possibility that observed GN-induced changes in PD and Isc were partially due to changes in membrane surface charge, the effects of GN in Cl- -free Ringer were studied. Under these conditions, GN had no effect on electrical parameters. Furthermore, GN elicited no effect on cAMP levels in either the presence or absence of glucose. These findings suggest that 1) the effect of GN on Jnet Cl is masked in the presence of glucose, 2) GN-induced increases in Isc and PD are a reflection of the increase in Jnet Cl and are neither due to changes in membrane surface charge nor to an increase in net Na+ flux, and 3) GN-induced secretory diarrhea is in part due to changes in electrolyte transport.

The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.

In vitro studies on H+ secretion, potential difference (PD), short-circuit current (Isc), and resistance across stripped mucosa of frog stomach in Cl-medium have shown that addition of nicotine in the serum bathing fluid caused a marked inhibition of the H+ secretory rate and an increase of PD and Isc without change of the transmucosal resistance. A dose-response correlation was indicated. During the first 8 min, the changes in the measured parameters, namely, PD versus Ih and Isc versus Ih, were linear. After 8 min, a deviation from linearity was observed. From the slope of the regression lines, the resistance of the electrogenic Cl- pump on the mucosal membrane (Rcl) was calculated to be 127 omega cm2 and the resistance of the chloride pathway on the serosal side (Rcl) was 407 omega cm2. The resistance of the H+ pump on the mucosal membrane (Rh) in Cl- medium was estimated to be 385 omega cm2. The sum of the emf's of the Cl+ pump on the mucosal membrane and of the Cl- gradient across the serosal membrane, namely Ecl + Ecl, was found to be 35 mV. The presence of such linear relationships between measured versus the H+ rate and Isc versus Ih lends support to the electrogenic theory of HCl secretion.