Depolarization increases inositolphosphate production in a particulate preparation from rat brain.
We have studied the accumulation of inositol phosphates (InsP) due to depolarization. A particulate preparation of rat brain was introduced to rule out transmitter activated mechanisms and to allow free access for drugs of high molecular weights. Potassium depolarization doubled InsP within a few minutes. InsP accumulation depended on time and K+ concentration, and was affected neither by tetrodotoxin nor by atropine. Radioactive metabolites co-eluted with inositol mono-phosphate and inositol bis-phosphate, whereas only minor amounts appeared with inositol tris-phosphate. The content in phosphatidylinositols was decreased. No evidence was found for the involvement of a neurotransmitter. Sea anemone toxin II (around 1 mumol/l), which keeps the Na+-channels open, promoted the InsP accumulation in an atropine-resistant manner. Tetrodotoxin prevented it when given before, and inhibited it when given after initiation by sea anemone toxin II. Moreover the K+ channel blockers 4-aminopyridine, dendrotoxin and tetraethylammonium all caused InsP accumulation. Palytoxin was by far the most potent promoter of InsP accumulation with a detection limit below 10 pmol/l, and displayed a unique bell-shaped concentration-effect correlation. Ouabain (3 mumol/l and above) also elicited the InsP accumulation. The response to carbachol was not only inhibited completely by atropine, but also partially (more than 50%) by tetrodotoxin, which indicates the involvement of voltage-dependent sodium channels in the receptor-triggered InsP accumulation. Thus independent of the causative agent, depolarization promotes an InsP accumulation. We conclude that degradation of phosphatidylinositols is mediated not only by receptor occupation but also by a positive shift in membrane voltage.
D000178:Acrylamides; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D003064:Cnidarian Venoms / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013403:Sugar Phosphates / Q000096:biosynthesis*; D014118:Toxins, Biological / Q000494:pharmacology; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D003064:Cnidarian Venoms; D007295:Inositol Phosphates; D007473:Ion Channels; D009467:Neuromuscular Depolarizing Agents; D010042:Ouabain; D011188:Potassium; D013403:Sugar Phosphates; D014118:Toxins, Biological; C010272:palytoxin; D000095702:Polyether Toxins