Na+/K+ATPase activity inhibition and isoform-specific translocation of protein kinase C following angiotensin II administration in isolated eel enterocytes

Abstract

In the eel, angiotensin II (Ang II) has a role at the level of both gill chloride and kidney tubular cells, regulating sodium balance and therefore osmoregulation. The present study extends these findings to another important osmoregulatory organ -the intestine. Enterocytes were obtained from sea-water (SW)-acclimated eels to investigate the role of Ang II on the intestinal Na + /K + ATPase activity, because in SW-acclimated animals the intestine represents an important site of water and NaCl transport from the mucosal to the serosal side. This paper demonstrates that isolated enterocytes stimulated with increasing Ang II concentrations (0·01-100 nM) showed a dosedependent inhibition of the Na + /K + ATPase activity. The threshold decrease was at 0·01 nM Ang II; it reached a maximum at 10 nM (81·5% inhibition) and did not decrease further with the use of higher hormone doses. These hormonal effects were blocked by a specific competitive antagonist of the AT1 receptor subtype, DuP-753 (100% inhibition at 10 µM), indicating that these effects are mediated by an AT1-like receptor. Isolated enterocytes stimulated with 10 nM Ang II showed a transient increase in intracellular calcium ([Ca 2+ ] i ), followed by a lower sustained phase. Removal of extracellular Ca 2+ did not reduce the initial transient response and completely abolished the plateau phase. The inhibition of the Na + / K + ATPase activity was dependent on protein kinase C (PKC) activation since PKC antagonists (calphostin C and staurosporine) abolished the inhibitory effect of Ang II, and the PKC activator phorbol 12-myristate 13-acetate reduced transporter activity. Western blot analysis with antibodies to PKC , I, II, , , ε, , and isoforms showed that eel enterocytes expressed the conventional isoforms ( and I), the novel isoforms ( and ) and the atypical isoforms ( and ). Ang II stimulated the translocation from the cytosol to the plasma membrane of PKC , PKC and PKC isoforms. In conclusion, our results suggest that Ang II modulates intestinal Na + /K + ATPase in SW-acclimated eels via calcium mobilization and PKC activation.

Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation

“…However, the underlying reason for the decreased Na ϩ -K ϩ -ATPase activity in IUGR placenta is still unknown. Angiotensin II has been shown to decrease Na ϩ -K ϩ -ATPase activity in several tissues (18,33,36,48), and our data indicate that angiotensin II is also a potent inhibitor of oubain-sensitive Na ϩ -K ϩ -ATPase activity in villous explants. Taken together, our data indicate that activation of the AT1-R by angiotensin II decreases placental system A amino acid transporter activity and suggests that enhanced placental RAS is a potential contributor to reduced system A amino acid transport in IUGR.…”

“…Recent studies (4,23) have demonstrated that Na ϩ -K ϩ -ATPase activity is decreased in IUGR. Na ϩ -K ϩ -ATPase activity is reportedly reduced by angiotensin II/AT1-R activation in several cell types, including glomerulosa cells and enterocytes (18,33,36,48).…”

Altered signaling pathways linked to angiotensin II underpin the upregulation of renal Na+-ATPase in chronically undernourished rats

“…those linked to AT 2 R [39,42] and ceramide receptors [49]. As discussed above, these alterations may be a consequence of increased local activity of Ang II in the tubulointerstitium, which can stimulate translocation of the upregulated PKCs to the membranes after binding to AT 1 R [50]. Even if small, the augmented abundance of AT 1 R would certainly contribute to an amplified, increased PKC-mediated activation of catalysis by the Na + pump.…”

Jejunal Dopamine and Na⁺,K⁺-ATPase Activity in Nephrotic Syndrome

“…Evidence has been gathered showing that ANP reduces fluid absorption in response to acute volume expansion [29], whereas both angiotensin II and angiotensin III can enhance intestinal electrolyte and fluid absorption in response to volume depletion [35]. In addition, angiotensin II was shown to modulate the intestinal Na + ,K + -ATPase activity via calcium mobilization and PKC activation [48]. In acute renal failure, an increase in serum aldosterone was suggested to stimulate the jejunal Na + ,K + -ATPase activity [49], whereas 5-hydroxytryptamine was found to increase Na + ,K + -ATPase activity in jejunal epithelial cells from young rats [50].…”