Brain natriuretic peptide modulates the delayed rectifier outward K(+) current and promotes the proliferation of mouse Schwann cells.
Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.Journal of Cellular Physiology (Impact Factor: 3.84). 02/2011; 226(2):440-9. DOI: 10.1002/jcp.22352
Brain natriuretic peptide (BNP) may act as a neuromodulator via its associated receptors (natriuretic peptide receptors, NPRs) in the central nervous system (CNS), but few studies have reported its activity in the peripheral nervous system (PNS). In this study, we observed that BNP increased the tetraethylammonium chloride (TEA)-sensitive delayed rectifier outward potassium current (I(K)) in mouse Schwann cells (SCs) using whole-cell recording techniques. At concentrations of 1-100 nM, BNP reversibly activated I(K) in a dose-dependent manner, with modulating its steady-state activation and inactivation properties. The effect of BNP on I(K) was abolished by preincubation with the specific antagonist of NPR-A, and could not be mimicked by application of NPR-C agonist. These results were supported by immunocytochemical findings indicating that NPR-A was expressed in SCs. The application of 8-Br-guanosine 3',5'-monophosphate (8-Br-cGMP) mimicked the effect of BNP on I(K), but BNP was unable to further increase I(K) after the application of cyclic guanosine monophosphate (cGMP). Genistein blocked I(K) and also completely eliminated the effects of BNP and cGMP on I(K). The selective K(V)2.1 subunit blocker, Jingzhaotoxin-III (JZTX-III), reduced I(K) amplitude by 30%, but did not abolish the increase effect of BNP on I(K) amplitude. In addition, BNP significantly stimulated SCs proliferation and this effect could be partly inhibited by TEA. Together these results suggest that BNP modulated I(K) probably via cGMP- and tyrosine kinase-dependent pathways by activation of NPR-A. This effect of BNP on I(K) in SCs might partly explain its effect on cell proliferation.
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ABSTRACT: To compare the therapeutic efficacy of recombinant human brain natriuretic peptide and prostaglandin E1 in the treatment of pulmonary hypertension after mitral valve replacement. Sixty patients with postoperative pulmonary hypertension were divided randomly into 3 groups that received saline, prostaglandin E1, and natriuretic peptide infusions for 12 hours each. The hemodynamics data were monitored consecutively, and the levels of thromboxane A2 and cyclic guanosine monophosphate were detected pretreatment, after treatment, and 1 week after surgery. The arterial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure decreased 1 hour after prostaglandin E1 treatment and rebounded after treatment discontinuation. The pulmonary arterial pressure and pulmonary capillary wedge pressure in the natriuretic peptide group decreased 3 hours after treatment; pulmonary arterial pressure decreased less than that of the prostaglandin group, and there was no evidence of hemodynamic rebound after treatment discontinuation. The natriuretic peptide had no significant effects on arterial pressure. In both the prostaglandin and natriuretic peptide groups, cyclic guanosine monophosphate increased after the treatment, which was even higher in the latter group. Prostaglandin E1 could lead to the decrease of thromboxane A2, which was not seen in the natriuretic peptide group. Both brain natriuretic peptide and prostaglandin E1 can effectively reduce pulmonary hypertension; however, natriuretic peptide has a slower and milder efficacy. The effects of these 2 drugs in reducing the pulmonary arterial pressure may be mediated through different pathways.
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ABSTRACT: Central nervous system (CNS) injury triggers production of myelinating Schwann cells from endogenous oligodendrocyte precursors (OLPs). These CNS Schwann cells may be attractive candidates for novel therapeutic strategies aiming to promote endogenous CNS repair. However, CNS Schwann cells have been so far mainly characterized in situ regarding morphology and marker expression, and it has remained enigmatic whether they display functional properties distinct from peripheral nervous system (PNS) Schwann cells. Potassium channels (K+) have been implicated in progenitor and glial cell proliferation after injury and may, therefore, represent a suitable pharmacological target. In the present study, we focused on the function and expression of voltage-gated K+ channels Kv1–12 and accessory β-subunits in purified adult canine CNS and PNS Schwann cell cultures using electrophysiology and microarray analysis and characterized their antigenic phenotype. We show here that K+ channels differed significantly in both cell types. While CNS Schwann cells displayed prominent K D-mediated K+ currents, PNS Schwann cells elicited K D- and KA-type K+ currents. Inhibition of K+ currents by TEA and Ba2+ was more effective in CNS Schwann cells. These functional differences were not paralleled by differential mRNA expression of Kv1–12 and accessory β-subunits. However, O4/A2B5 and GFAP expressions were significantly higher and lower, respectively, in CNS than in PNS Schwann cells. Taken together, this is the first evidence that CNS Schwann cells display specific properties not shared by their peripheral counterpart. Both Kv currents and increased O4/A2B5 expression were reminiscent of OLPs suggesting that CNS Schwann cells retain OLP features during maturation.
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