SCN-and HSCN transport through lipid bilayer membranes. A model for SCN- inhibition of gastric acid secretion.

Diffusion of thiocyanate (SCN-) and thiocyanic acid (HSCN) (pK=-1.8) through lipid bilayer membranes was studied as a function of pH. Membranes were made of egg phosphatidylcholine or phosphatidylcholine plus cholesterol (1:1 mol ratio) dissolved in decane or tetradecane. Tracer fluxes and electrical conductances were used to estimate the permeabilities to HSCN and SCN-. Over the pH range 1.0 to 3.3 only HSCN crosses the membrane at a significant rate. The relation between the total SCN flux (JA), concentrations and permeabilities is: 1/JA = 1/pul([A-]+[HA])+1/pm HA[HA], where [a-] and [HA] are the concentrations of SCN- and HSCN, pul is permeability coefficient of the unstirred layer, and PmHA is the membrane permeability to HSCN. By fitting this equation to the data we find that PmHA = 2.6 cm.s-1 and Pul = 9.0.10-4 cm .s-1. Conductance measurements indicate that PmA- is 5.10-9 cm.s-1. Addition of cholesterol to phosphatidylcholine (1:1 mol ratio) reduces PmHA by a factor of 0.4 but has no effect on PmA-. SCN- is potent inhibitor of acid secretion in gastric mucosa, but the mechanism of SCN- action is unknown. Our results suggest that SCN- acts by combining with H+ in the mucosal unstirred layer (secretory pits) and diffusing back into the cells as HSCN, thus dissipating the proton gradient across the secretory membrane. A similar mechanism of cation is proposed for some other inhibitors of gastric acid secretion, e.g. nitrite (NO2-), cyanate (CNO-) and NH4+.