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Use‐Dependent Suppression of the Nicotinic Acetylcholine Receptor Response by the Proadrenomedullin N‐Terminal 20‐Amino Acid Peptide in Rat Locus Coeruleus Neurons
Author(s) -
Nabekura Junichi,
Murata Osamu,
Ishibashi Hitoshi,
Akaike Norio
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020865.x
Subject(s) - mecamylamine , hexamethonium , acetylcholine , nicotinic agonist , medicine , endocrinology , chemistry , nicotinic acetylcholine receptor , nicotine , locus coeruleus , acetylcholine receptor , receptor , biology , central nervous system
The effects of the proadrenomedullin N‐terminal 20‐amino acid peptide (PAMP) on the nicotinic acetylcholine (ACh) receptor (nAChR)‐mediated inward current were investigated in neurons acutely dissociated from the rat locus coeruleus using whole‐cell recording under voltage clamp. Nicotine and cytidine mimicked the ACh response, whereas the maximal response to dimethyl‐phenylpiperazinium was lower in amplitude compared with that to ACh. Nicotine‐induced current ( I nic ) was suppressed more effectively by mecamylamine than by hexamethonium. In addition, neither atropine nor α‐bungarotoxin affected the I nic . PAMP reversibly and noncompetitively suppressed the peak amplitude of 10 −4 M I nic . PAMP concentrations for the threshold, half‐maximal inhibition, and maximal inhibition of 10 −4 M I nic were 10 −8 , 2.6 × 10 −7 , and 10 −5 M , respectively. The peak amplitudes of 10 −4 M I nic elicited at 2‐min intervals showed a gradual decline in the presence of 10 −7 M PAMP. This decline in the I nic was independent of the period of PAMP pretreatment. The suppression of I nic by PAMP did not show any voltage dependency at a holding potential ( V H ) of <0 mV, although the inhibitory effect was masked by the marked inward rectification of I nic at a V H of 0 mV. These results suggest that PAMP could thus be a unique endogenous peptide that antagonizes the nAChR in the CNS.