Mechanisms of oxalate absorption and secretion across the rabbit distal colon

Abstract

To further evaluate the mechanisms of oxalate (Ox²⁻) transport in the intestine the following studies were performed using isolated, short-circuited segments of the rabbit distal colon (DC). In control buffer, the DC absorbed Ox²⁻ (net Ox²⁻ flux, J ^Ox_Net =5.4±0.7 pmol · cm⁻² · h⁻¹). Replacement of Na⁺ with N-methyl-d-glucamine (NMDG⁺) abolished Ox²⁻ absorption by decreasing mucosal to serosal Ox²⁻ flux (J ^Ox_ms ), without affecting Cl⁻ transport, while gluconate substitution for Cl⁻ did not affect J ^Ox_Net or net Na⁺ flux (J ^Na_Net ). Addition of Na⁺ to the serosal side of tissues bathed by NMDG⁺ buffer increased J ^Ox_ms 40% without altering mucosal to serosal Cl⁻ flux (J ^Cl_ms ). Serosal amiloride or dimethyl amiloride (10⁻³ M) abolished J ^Ox_Net by decreasing J ^Ox_ms , it increased serosal to muscosal Cl⁻ flux (J ^Cl_sm ) and it gradually inhibited short-circuit current (I _sc). Mucosal amiloride (10⁻⁴ M) abolished I _sc but had no effect on Ox²⁻ or Cl⁻ fluxes. Serosal 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS, 10⁻⁶ M) reduced J ^Ox_ms by 20% and J ^Ox_Net by 43% without affecting J ^Cl_ms or J ^Cl_Net . Dibutyryl cyclic adenosine monophosphate (dB-cAMP, 5×10⁻⁴ M, both sides) stimulated Ox²⁻ secretion (J ^Ox_Net = −12.6±3.3 pmol · cm⁻² · h⁻¹). The dB-cAMP-induced secretion of Ox²⁻ and Cl⁻ were fully abolished by serosal furosemide (10⁻⁴ M) and partially inhibited (35%) by 5×10⁻⁴ M mucosal NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid], a putative Cl⁻ channel blocker. It is proposed that: (1) basal absorption of Ox²⁻, but not Cl⁻, is dependent upon a previously undescribed basolateral Na⁺-H⁺ exchanger that may be coupled to a DIDS-sensitive, basolateral anion exchange system that mediates Ox²⁻ flux; (2) the DC secretes Ox²⁻ in response to dB-cAMP by a mechanism that is indistinguishable from the pathway for Cl⁻ secretion.