Brain natriuretic peptide stimulates K and Cl secretion across porcine distal colon epithelium

Porcine distal colon epithelium was mounted in Ussing chambers and bathed with porcine Ringer solution. The serosal addition of brain natriuretic peptide (BNP; 50 nM) or atriopeptin III (AP-III; 500 nM) produced significant increases (50-75 μA/cm²) in short-circuit current (I(sc)). These increases in I(sc) were not inhibited by pretreatment with tetrodotoxin (TTX) or 5,8,11,14-eicosatetraynoic acid (ETYA). Analysis of concentration-response relationships revealed that BNP was 5.8-fold more potent than AP-III in stimulating the I(sc). BNP and AP-III significantly increased the serosal-to-mucosal (S→M) Cl flux and reduced net Cl absorption by 38 and 41%, respectively. The BNP-stimulated S→M Cl flux was abolished when HCO₃ was removed. In contrast, the vasoactive intestinal peptide (VIP)-stimulated S→M Cl flux was not affected by HCO₃ replacement. In addition to their effects on Cl transport, BNP and AP-III increased net Rb secretion by 79 and 58%, respectively. BNP-stimulated Rb secretion was reduced by 76% after HCO₃ replacement. These results indicate that natriuretic peptides stimulate K- and HCO₃-dependent Cl secretion which is not present under basal conditions or after VIP stimulation. The difference in potency between BNP and AP-III suggests that ANP-B receptors may mediate their effects on ion transport in the porcine colon.