Na-+,K+ ATPase inhibitor

Cells are normally kept at osmotic (water activity) equilibrium by the action of the Na-pump. Inhibition of the pump with the specific Na -K -ATPase inhibitor, ouabain, causes cell swelling as does inhibition of it by hypothermia. The intracellular environment contains a high concentration of K (100 to 120 mM, in most mammalian cells), lower concentrations of Na (about 10 to 30 mM), and high... 

Results similar to those reported for co-conotoxin GVIA were obtained with the Na+, K+-ATPase inhibitor-I (10) J67 a 49 amino acid residue peptide containing four intramolecular disulfide bonds (Scheme 5)J681 Even in this case the addition of redox reagents to the oxidation buffer had a minor effect on the product distribution. 

The reduced form of Na+, K+-ATPase inhibitor-I (10) was obtained by treatment of the protected peptide synthesized by the soln procedure with HF, followed by reaction with Hg(OAc)2. After purification of the crude product on Sephadex G-25, the reduced peptide (110 mg) was dissolved in 0.1 M NH4OAc buffer (1L, pH 7.8) at a peptide concentration of 0.018 mM and then stirred at rt. After 24 h, the major peak in the HPLC, which coeluted with the natural product, corresponded to 55% of the product distribution. The mixture was acidified to pH 3 with AcOH and 10 was purified by RP-HPLC. When the oxidation was carried out in the presence redox reagents at a peptide/GSH/GSSG ratio of 1 100 10, after 24 h the major oxidation product increased to 69%. The mixture was acidified with AcOH and the product (10) isolated by preparative HPLC yield 20%. The product was characterized by MALDI-TOF-MS and amino acid analysis a combination of enzymatic peptide mapping and synthetic approaches were applied to assign the cystine connectivities. 

Okamoto, Y. Ojika, M. Sakagami, Y. (1999) lanthaan A, a dimoic polybrominated benzofuran as a Na,K-ATPase inhibitor from a marine sponge, lanthella sp. Tetrahedron Lett., 40, 507-10. 

A hexaprenyl-hydroquinone sulfate (395) was identified as an H+/K+-ATPase inhibitor from a Japanese species of Dysidea [339]. Sarcotragus spinulosus from deep water contained the Na+/K+-ATPase inhibitors sarcochromenol sulfates A-C (396-398) and sarcohydroquinone sulfates A-C (399-401) [340]. The structures were determined by spectral data analysis of the natural products and of derivatives. 

Iantherans A (516) and B (517) are dimeric tetrabrominated benzofuran derivatives that were isolated from an Australian Ianthella species. The structures were determined by spectroscopic and chemical methods. Iantheran A (516) includes a (Z,Z)-1,3-butadiene moiety, whereas iantheran B (517) is the geometric isomer possessing a (Z, )- 1,3-butadiene moiety. Both compounds were Na+/K+-ATPase inhibitors [434,435]. Ianthesines C (518) and D (519) showed potent Na+/K+-... 

Figure 30-16 Structures of some neurotoxins that affect ion channels. Other neurotoxins include the Na+, K+-ATPase inhibitor ouabain (Fig. 22-12), batrachotoxin (Fig. 22-12), and picrotoxin (Fig. 22-4). The structure of a scorpion toxin is from Almassy et al.,i9ia that of to conotoxin is from Pallaghy et al.,i35 and that of brevetoxin is redrawn after Shimizu et al.i36...

Okamoto Y, Nitanda N, Ojika M, Sakagami Y (2001) Aplysiallene, a New Bromoallene as an Na, K-ATPase Inhibitor from the Sea Hare, Aplysia kurodai. Biosci Biotechnol Biochem 65 474... 

Okamoto Y, Ojika M, Sakagami Y (1999) Iantheran A, a Dimeric Polybrominated Benzo-furan as a Na,K-ATPase Inhibitor from a Marine Sponge, lanthella sp. Tetrahedron Lett 40 507... 

Dubyak, G.R. and A. Kleinzeller. 1980. The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as a (Na+-K+)ATPase inhibitor. The J. Biol. Chem. 255 5306-12. 

Lanoxicap Digoxin 50, 100, 200 (jLg SEC Heart failure, atrial fibrillation Na-K ATPase inhibitor PEG 400, ethyl alcohol, propylene glycol, purified water GSK... 

Na+ gradient across the cell membrane, as evidenced by the effects of the Na+,K+-ATPase inhibitor ouabain [104]. 

Herbal medicinal traditions can be traced back to our primate forebears. Thus, parasite-infected chimpanzees make recourse to particular plants, which they evidently associate with symptomatic relief. Human cultures in general have accumulated medicinal protocols based on use of plants, major traditions including Chinese medicine and Indian Ayurvedic herbal medicine. As detailed in this book, in some instances, specific bioactive substances from medicinal plants (or derivatives of such compounds) have found application in conventional medicine. Thus, the cardiotonic cardiac glycoside sodium pump (Na+, K+-ATPase) inhibitors derived from the initial use for cardiac insufficiency of digitalis (dried leaves of the foxglove, Digitalis purpuremri). 

D-Bornyl acetate (= Borneol acetate) (monoterpene) Cardenolides (triterpene glycosides aglycones) see Table 4.1 for cardenolide Na+, K+-ATPase inhibitors Citral (= mixture of a-Citral (Geranial) (3-Citral (Neral) = trans-St av-3,7-Dimethyl-2,6-octadienal) (monoterpene) Citronellal (= 3,7-Dimethyloct-6-enal) (monoterpene) a-Farnesene (sesquiterpene)... 

Coumarins and furanocoumarins, which serve as potent defence compounds in the Apiaceae and Rutaceae, occur in a few, mostly unrelated, species. Only in the genus Psoralea do they have a wide distribution. An-thraquinones, which are potent Na+, K+-ATPase inhibitors and strong purgatives, occur widely in the genus Cassia (Senna), but otherwise only occasionally in Andira and Abrus. 

Cantley LC Jr, Josephson L, Warner R, et al. 1977. Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. J Biol Chem 252 7421-7423. 

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