alpha Latrotoxin of black widow spider venom binds to a specific receptor coupled to phosphoinositide breakdown in PC12 cells.
alpha Latrotoxin of black widow spider is known to bind with high affinity to surface sites of rat pheochromocytoma (PC12) cells, thereby causing depolarization, calcium influx and massive neurotransmitter release. We show here that the toxin causes the accumulation of inositol phosphates, the products of phosphoinositide breakdown. Inositol 1,4,5, trisphosphate was predominantly accumulated shortly after toxin application. Phosphoinositide breakdown appears to be a direct consequence of toxin binding because high K+ and ionophores (which induce depolarization, calcium influx and transmitter release by different mechanisms) were without such effect. Phosphoinositide breakdown is known as an event coupled to the activation of receptors of various hormones and transmitters. We suggest therefore that the alpha latrotoxin binding site is a receptor coupled across the membrane to the phosphoinositide hydrolysing system.
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001180:Arthropod Venoms / Q000378:metabolism*; D001740:Black Widow Spider; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018377:Neurotransmitter Agents / Q000378:metabolism; D010673:Pheochromocytoma; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D018000:Receptors, Peptide; D013111:Spider Venoms / Q000378:metabolism*
D001180:Arthropod Venoms; D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D011950:Receptors, Cholinergic; D018000:Receptors, Peptide; D013111:Spider Venoms; C034800:alpha-latrotoxin receptor; C020763:alpha-latrotoxin; D002118:Calcium