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Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission
Author(s) -
Akasu T.,
Kojima M.,
Koketsu K.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb11057.x
Subject(s) - acetylcholine , acetylcholine receptor , nicotinic agonist , medicine , chemistry , endocrinology , bullfrog , reversal potential , substance p , neuromuscular transmission , nicotinic acetylcholine receptor , receptor , cholinergic , biophysics , biology , patch clamp , biochemistry , neuropeptide
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 μ M ). 3 The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 μ M ). 4 Substance P (4.2 μ M ) 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 μ M ) 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.