Differing mechanisms of stimulation of Na+ absorption in rabbit proximal colon.

Both alpha2-adrenergic agonists and decreased Na+ in the bathing fluids stimulate electroneutral Na+ absorption in rabbit proximal colon, but it is unclear whether they have similar modes of action. We sought to define regulatory events involved with stimulation of Na+ absorption by these two agonists. Transport parameters were assessed by ion flux studies under short-circuit and pH stat conditions, recordings of intracellular electrical potential difference (psi(mc)) with microelectrode impalements, and measurement of intracellular pH (pH(i)). Epinephrine elicited a yohimbine-inhibitable alkalinization of pH(i) but did not alter psi(mc) In contrast, lowered serosal Na+ concentration ([Na+]) did not significantly increase pH(i) but did depolarize psi(mc). Removal of serosal HCO(3)- stimulated Na+ absorption and reversed residual ion flux from secretion to absorption. pH stat studies demonstrated epinephrine-stimulated, amiloride-inhibitable serosal alkalinization. Serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibited Na+ absorption. Epinephrine and lowered [Na+] have different effects on intracellular parameters associated with electroneutral Na+ absorption. Epinephrine stimulates an apical Na+/H+ exchanger. Lowered [Na+] elicits responses consistent with a coupled Na+-HCO(3x)- exit step. Coordinated function of apical Na+/H+ exchangers and a basolateral Na+-HCO(3)(x)- symport permit Cl(-)-independent electroneutral Na+ absorption while maintaining pH(i) homeostasis. Given the low [Cl-] environment of the colonic lumen, this transport pathway may be important for electroneutral Na+ absorption.