抄録
Nitric oxide (NO) possesses a variety of biological actions in the kidney, including regulation of renal hemodynamics, renin secretion and tubular transport of solutes and water. However, effects of NO on the K channel activity in proximal tubule cells have not been elucidated. We recently reported that NO had a biphasic effect on activity of a 40 pS K channel in cultured human proximal tubule cells. In this study, we tried to clarify which isoforms of NO synthase (NOS) were involved in the endogenous production of NO and modulation of the K channel activity, using the cell-attached mode of the patch-clamp technique and RT-PCR. Under the control condition, a NOS substrate, L-arginine (500μM), increased channel activity, which was abolished by an nNOS/iNOS-specific inhibitor, TRIM (100μM). Consistent with this observation, mRNA expression of iNOS alone was detected by RT-PCR. However, after the cells were incubated with atrial natriuretic peptide (ANP, 300nM) for 24 h, eNOS expression was also evident. In addition to this long-term effect, ANP increased channel activity within 5 min under the control condition, which was not affected by TRIM or an inhibitor of soluble guanylate cyclase (ODQ, 10μM), suggesting that the acute stimulatory effect of ANP would be independent of the NO pathway. In conclusion, iNOS is the major source of endogenous NO in cultured human proximal tubule cells under the control condition, whereas eNOS also participates after prolonged exposure to ANP. [Jpn J Physiol 55 Suppl:S68 (2005)]
