Substance P enhances cholinergic receptor desensitization in a clonal nerve cell line.
Substance P inhibits carbamylcholine-induced 22Na+ uptake in the clonal cell line PC12. This inhibition is noncompetitive with agonist but competitive with Na+. Octahydrohistrionicotoxin (H8-HTX) also exhibits this same pattern of inhibition. Moreover, both substance P and H8-HTX are very effective in enhancing agonist-induced receptor desensitization. Local anesthetics, such as QX222, also cause inhibition that is competitive with Na+, but they have only marginal effects on desensitization. Because substance P and H8-HTX cannot by themselves cause desensitization, their action is dependent on and synergistic with the action of agonist. Furthermore, substance P and H8-HTX do not appear to compete for the same site as QX222, which is thought to bind to the ion channel. Finally, substance P can stabilize the desensitized state of the receptor even when added subsequent to the actual desensitization and removal of agonist. Thus, substance P does not require open ion channels for binding and may modulate the activity of the receptor-ionophore complex by binding to a distinct regulatory site.
D000664:Amphibian Venoms / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors; D002460:Cell Line; D002999:Clone Cells; D007473:Ion Channels / Q000187:drug effects; D007700:Kinetics; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*
D000664:Amphibian Venoms; D000779:Anesthetics, Local; D007473:Ion Channels; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D013373:Substance P; D002217:Carbachol; D012964:Sodium