THE EFFECT OF COLCHICINE ON PROXIMAL TUBULAR REABSORPTION

Abstract

Aquaporins, expressed in the brush border membrane (BB) could play a pivotal role in glomerulo-tubular balance (GTB) by effecting adaptive changes of water permeability to the variations in the load of filtered solutes. Since aquaporin expression is modulated by microtubule-dependent trafficking between endoplasmic reticulum and cell membranes, we used the microtubule poison colchicine to assess the importance of aquaporins in mediating GTB. The effects of colchicine 1.6×10−4m on proximal tubule volume reabsorption was tested on 48 nephrons of ten rats by micropuncture techniques. Thirty proximal tubules were sampled from the last proximal convolution before, and recollected during and again after the microinjection (MIJ), into the early proximal convolution or Bowman's space, of colchicine added to a Ringer solution. We studied 18 proximal tubules in the same way before, during and after the microperfusion (MP) of colchicine added to an ultrafiltrate of plasma into the peritubular capillaries. During MIJ, SNGFR did not change significantly from baseline (17.7±1.3 vs 20.9±1.8 nl min−1, P>0.12). Post-control values were superimposable upon their paired pre-MIJ controls, when available (15.8±1.3 vs 13.5±1.5 nl min−1, P>0.25). The measurements of percentage reabsorption (49±5 during baseline, 45±7 during MIJ, and 55±5 in post-control, P>0.6) and absolute reabsorption (8.1±0.7, 11.1±2.2, and 7.9±1.3 nl min−1, respectively, P>0.18) were also unchanged. The three average measurements obtained in control conditions, during MP and again in post-MP control were not significantly different for SNGFR (19.8±3.0, 20.0±4.7, and 20.2±3.5 nl min−1, P>0.48), percentage (55±3, 59±5, and 47±3%, P>0.35) and absolute reabsorptions (12.5±2.2, 12.4±4.6, and 9.4±1.0 nl min−1, respectively, P>0.42). MIJ and MP of vehicles were devoid of any measurable effect. Colchicine does not acutely affect volume reabsorption in the proximal tubule. Aquaporin trafficking, if any, is not involved in mediating glomerulotubular balance in the proximal tubule, although aquaporin expression and function could still be important, although regulated by mechanisms different from microtubule-dependent shuttling between endoplasmic reticulum and BB.