Effect of alamethicin, gramicidin S and melittin upon the particulate guanylate cyclase from rat lung.
The channel-forming antibiotic alamethicin activated rat lung particulate guanylate cyclase (GTP pyrophosphate-lyase (cyclizing) EC 4.6.1.2), and the activated enzyme was further stimulated by sodium nitroprusside when a thiol such as 2-mercaptoethanol was present. Similar effects were seen with the antibiotic gramicidin S and with melittin, a polypeptide purified from bee venom. All of these agents are amphiphilic polypeptides. Nitroprusside was not able to stimulate both particulate and soluble enzyme treated with the nonionic amphiphile, Lubrol PX, suggesting that the membrane-active polypeptides had a different mechanism of action. These polypeptides are known to alter the membrane matrix by binding to phospholipid, and we suggest that this alteration allowed greater access of substrate and of nitroprusside to the enzyme. Lubrol PX, however, may interact preferentially with the enzyme, and thus block nitroprusside activation. The most potent of these agents was melittin, which stimulated nitroprusside activation at a concentration which had little effect by itself (7 microns), and at which others have demonstrated lytic effects on cells.
D000408:Alamethicin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001514:Bee Venoms / Q000494:pharmacology*; D004789:Enzyme Activation; D006096:Gramicidin / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D008623:Mercaptoethanol / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats
D000900:Anti-Bacterial Agents; D001514:Bee Venoms; D006096:Gramicidin; D009599:Nitroprusside; D008555:Melitten; D000408:Alamethicin; D008623:Mercaptoethanol; D006162:Guanylate Cyclase