Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.
The action of arecoline on rat locus coeruleus neurons was studied by intracellular recording from the in vitro brain slice preparation. Superfusion of arecoline (0.1-100 microM) caused two dose-related effects, an increased firing rate and, in neurons previously hyperpolarized to a constant potential by passing a steady hyperpolarizing current across the membrane, depolarization. Both effects were associated with a reduction in membrane input resistance. Moreover, the arecoline-induced excitatory effects were antagonized by the muscarinic receptor antagonist, atropine, but not by the nicotinic receptor antagonist, hexamethonium. Methoctramine, a selective M2-muscarinic receptor antagonist, was also effective in reversing the arecoline-induced effects, with a dissociation equilibrium constant of 14.2+/-1.2 nM (n=6). These results therefore suggest that arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus.
Yang
Y R
YR
Faculty of Physical Therapy, National Yang-Ming University, Taipei, Taiwan, ROC.
Chang
K C
KC
Chen
C L
CL
Chiu
T H
TH
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003959:Diamines / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology
D018679:Cholinergic Agonists; D003959:Diamines; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D018738:Hexamethonium; D001115:Arecoline; D001285:Atropine; C054938:methoctramine