Both substance P agonists and antagonists inhibit ion conductance through nicotinic acetycholine receptors on PC12 cells

Substance P stimulates substance P receptors but also inhibits ion conductance through nicotinic acetylcholine receptors. Substance P analogs, classified as agonists or antagonists based on their actions on smooth muscle, were tested to determine if they also could act at nicotinic receptors on the pheochromocytoma, PC12. All of the analogs tested, [D-Pro², D-Trp^7,9]SP, [D-Arg¹, D-Pro², D-Trp^7,9, Leu¹¹]SP, [pGlu⁵, MePhe⁸, Sar⁹]SP-(5-11), and [D-Pro⁴, D-Trp^7,9,10]SP-(4-11), inhibited agonist-induced uptake of ⁸⁶Rb⁺ through the nicotinic receptors at concentrations quite similar to those required for action at substance P receptors on smooth muscle. Thus, the chemical modifications in the analogs do not substantially alter their ability to inhibit nicotinic receptors.