title: Effects of substance P on nicotinic acetylcholine receptor function in PC12 cells.
abstract: The effects of substance P on the functioning of nicotinic acetylcholine receptors in PC12 cells were examined. Carbachol-stimulated 22Na+ uptake was used to assess the functional state of the nicotinic receptor. We found that incubation of the cells with substance P alone caused a loss of receptor function. Receptors recovered from this effect with a t1/2 of 0.94 +/- 0.10 min. Since receptors recovered from carbachol-induced desensitization at a significantly slower rate (t1/2, 1.77 +/- 0.21 min), it was concluded that the two inactive states are not kinetically equivalent. The effects of substance P on carbachol-induced loss of receptor activity were also examined. Substance P had no effect on a component of carbachol-induced loss of activity that was nonrecoverable (inactivation). However, substance P had several effects on the recoverable loss of activity induced by carbachol (desensitization). Substance P caused a shift to the left in the EC50 for carbachol-induced desensitization at equilibrium. If cells were simultaneously incubated with carbachol and substance P7-11, a low-potency analog of substance P, an increase in the rate of formation of a state of the receptor that was kinetically indistinguishable from the state induced by carbachol alone was observed. However, not all inhibition of nicotinic cholinergic function could be explained by an increased rate of formation of a desensitized receptor and it is concluded that substance P causes both enhanced desensitization and block of the nicotinic receptor-linked channel.
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D010673:Pheochromocytoma / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*
chemical_list: D011978:Receptors, Nicotinic; D013373:Substance P; D002217:Carbachol