Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission.
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. 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 microM). The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 microM). Substance P (4.2 microM) 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 (Vmax) without changing the apparent affinity (Km) of ACh for the receptor. Substance P (0.42-42 microM) 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. 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. 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.
D000818:Animals; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011898:Ranidae; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*
D011950:Receptors, Cholinergic; D013373:Substance P