Abstract
To investigate the effects of muscarinic receptor agonisits on area postrema (AP) neuronal activity, we performed whole-cell recordings from neurons in rat brain slices. Excitatory responses were found in 44% (22/50) of cells tested during the bath application of cevimeline (M3 receptor selective agonist, up to 500 μM). Voltage-clamp recordings showed a marked inward current without an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) (n=18). Such responses were found in either major electrophysiological cell classes, i.e. cells displaying Ih and cells not displaying Ih. Current-clamp recordings showed cevimeline-induced depolarization of membrane potential that modulated the frequency of action potentials (n=4/10). In 3 cells showed cevimeline-induced inward currents, bath-applied pilocarpine (a partial agonist at the M3 and M5 receptors) elicited a decrease in the frequency of mEPSCs (from 1.0 ± 0.2 Hz to 0.5 ± 0.1 Hz). These results suggest that M3 receptors are present in the post- and/or extrasynaptic regions of AP neurons and M5 receptors are present in the presynaptic nerve terminals. A side effect of cevimeline for dry mouth patient, such as nausea and vomiting, may be triggered by the activation of M3 receptors in AP neurons. [J Physiol Sci. 2008;58 Suppl:S158]
