Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission

Abstract

1 The effect of substance P on the sensitivity of nicotinic acetylcholine (ACh) receptors of bullfrog sympathetic ganglion cells and frog skeletal muscle endplate was examined electrophysiologically. 2 The amplitude of ACh-induced postsynaptic potential (ACh potential) and current (ACh current) were reversibly and dose-dependently reduced by substance P at low concentrations (0.42–42 μM). 3 The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 μM). 4 Substance P (4.2 μM) shifted the S-shaped dose-response curve of the ACh current downward. A Lineweaver-Burk plot constructed from the dose-response curve revealed that substance P depressed the maximum response without changing the apparent affinity (K_m) of ACh for the receptor. 5 Substance P (0.42–42 μM) did not alter the reversal potential of the ACh current of the endplate. The half-decay time of endplate current (e.p.c.) and its voltage-dependency were not altered by substance P in these concentrations. 6 The depression of the ACh current by substance P may not be due to a blockade of the opened channel which has been activated by the preceding combination of ACh with the receptor. 7 These results suggest that substance P suppresses the sensitivity of nicotinic ACh-receptors of the sympathetic ganglion cell and skeletal muscle endplate, acting on a certain allosteric site but not the recognition site of ACh in the receptor-ionic channel complex.