Vectorial efflux of cGMP and its dependence on sodium in the cortical collecting duct

Guanosine 3',5'-cyclic monophosphate (cGMP) is an important second messenger that regulates transport in the nephron. We propose that the transport mechanisms that remove cGMP from the cell are different in the luminal and basolateral membranes of the cortical collecting duct (CCD). We examined efflux of cGMP from cultured and isolated perfused CCDs in response to atrial natriuretic factor (ANF) and nitric oxide (NO). In the presence of phosphodiesterase inhibition, these compounds resulted in preferential efflux of cGMP across the basolateral membrane in both cultured and isolated CCDs. In the presence of ANF, efflux was five times higher across the basolateral than the luminal membrane in cultured CCD cells (n = 14). In isolated CCDs, effluxes across the basolateral and luminal membranes were 1.02 +/- 0.2 and 0.03 +/- 0.01 fmol.mm-1.min-1, respectively, in the presence of ANF (n = 6; P < 0.007) and 0.87 +/- 0.21 and 0.02 +/- 0.01 fmol.mm-1.min-1, respectively, in the presence of NO (n = 6; P < 0.011). Efflux across the basolateral membrane in the presence and absence of sodium was 37 +/- 7.3 and 19.9 +/- 5 fmol.cm-2.min-1, respectively, in cultured cells (n = 12; P < 0.044) and 1.02 +/- 0.2 (n = 6) and 0.41 +/- 0.12 (n = 5) fmol.mm-1.min-1 in isolated perfused tubules (P < 0.042). There was no difference in luminal transport in the presence and absence of sodium in either model. We conclude that there are at least two different mechanisms involved in the removal of cGMP from the cell, one sodium dependent and the other sodium independent. The basolateral membrane appears to contain both, whereas the luminal membrane contains only the sodium-independent mechanism.