Intestinal transport of weak electrolytes: Determinants of influx at the luminal surface.

Abstract

A B S T R A C T The determinants of weak electrolyte influx into everted segments of rat small intestine have been studied. Preliminary experiments showed that the observed influxes could be described as unidirectional, diffusional fluxes of the nonionized compound uncomplicated by a parallel ionic component. It is shown that the determinants of weak electrolyte influx in this situation may be described in terms of the resistance of the unstirred layer to movement from the bulk phase to the cell surface, the degree of ionization of the weak electrolyte at the cell surface, and the cellular permeability to the nonionized weak electrolyte. Quantitative considerations indicated that the unstirred layer was totally rate-limiting in the cases of some poorly ionized, or highly permeant compounds, but the unstirred layer was not totally rate limiting for most of the compounds studied. Calculation of cellular permeabilities for the nonionized forms of weak electrolytes required assumptions to be made concerning the pH value in the surface fluid layer. A uniform set of permeability data including both weak acids and weak bases was obtained only when it was assumed that the pH in the surface fluid layer was equal to that in the bulk phase, and it was concluded that these studies do not support the concept of a micr6i:limate of distinctive pH at the epithelial surface as a determinant of weak electrolyte transport.In 1959 Hogben et al. (5) found that the steady-state distributions of weak electrolytes across the wall of the small intestine could not be described in terms of a two-compartment, pH partition model. A possible explanation of this discrepancy was based on the observation that the acid-base metabolism of the intestinal epithelium is asymmetric (16, 17). Hogben et al. (5) proposed that the secretion of hydrogen ions into the luminal fluid leads to the formation of a region of low pH at the epithelial surface. In this situation the distribution of a weak electrolyte between ionized and nonionized forms in the surface "microclimate" is different from the distribution in the luminal bulk phase, and Hogben et al. (5) suggested that the transmural distributions of weak electrolytes are determined by the concentrations of the permeant, nonionized species at the epithelial surface. The experiments described here were intended to test the suggestion that the intestinal transport of weak electrolytes is influenced by a region of distinctive pH at the luminal surface of the epithelium. Comparison

Inhibition of cortical collecting tubule chloride transport by organic acids.

“…To determine whether the inhibitory effect of these compounds on Cl self-exchange is specific for organic acids, we first examined the effect of naloxone on Kcj. Naloxone is an organic base, but its KIhloro is reasonably close to that of iso-butyrate (about 2.0 X 10-1) (20). As shown in Table IV, 1 mM naloxone had no effect on Ka2.…”

“…Partition coefficients in chloroform/aqueous phase systems (KhorO) were determined for nonionic forms of several organic acids, and in olive oil/aqueous and ether/aqueous for iso-butyrate using a modified radiotracer method previously described (20). In general, I ml of aqueous solution, pH 1.5 containing 0.03-0.07 ACi of '4C-labeled organic acids was mechanically shaken with 3 ml of nonaqueous phase solution for 1 h at room temperature.…”

“…'4C counts per minute were converted to disintegrations per minute using measured counting efficiencies in water and the nonaqueous phase liquid. Partition coefficients (Kp) for undissociated forms of organic acids were calculated according to formulae previously described (20); the calculations shown below use the example of the chloroform/aqueous partition coefficient: Kr'°= r (1 + 100"), where r = 14C (dpm)/ml in chloroform phase/'4C (dpm)/ml in aqueous phase, and a = pH (aqueous phase) -pKa. pKa is the dissociation constant for the organic acid being examined.…”

“…ciated organic acids and bases (Ihl°r') have been previously determined by Jackson et al (20). Using the methods they described, we determined partition coefficient values for several organic acids whose values were not available (Table II).…”

The effect of E. coli STa enterotoxin on the absorption of weakly dissociable anti‐malarial drugs from rat intestine in vivo

“…Application of an unstirred layer correction to the experimental data A proposed (Jackson et al, 1978) equation for flow of charged and uncharged forms across an unstirred layer followed by uptake of the uncharged form only is:-(= P.; +D (1) where J" , the flux of neutral species past the membrane from compartment 2 (the unstirred layer) into compartment 3 (the mucosa), is related to the bulk phase concentration C1 and an empirical permeability coefficient; this consisting of an unstirred layer term where D is the diffusion coefficient of both neutral and ionised forms and is the unstirred layer thickness, and a membrane permeability term Pi for the neutral form adjusted for the degree of dissociation (1 + 102) where a2 = pKa-pH2, the dissociation constant of the weak base minus pH2, the pH within the unstirred layer i.e. the microclimate immediately next to the mucosal membrane.…”