Adenosine A1 receptors modulate the discharge activities of inspiratory and biphasic expiratory neurons in the medial region of Nucleus Retrofacialis of neonatal rat in vitro.

This study investigated whether adenosine A1 receptors could modulate respiratory rhythm in mammals. Experiments were performed in in vitro brainstem slice preparations from neonatal rats. These preparations included the medial region of Nucleus Retrofacialis (mNRF) with the hypoglossal nerve (XII nerve) rootlets retained. The rhythmical discharges of the biphasic expiratory (biphasic E) neurons/inspiratory neurons (I neurons) and activities of the XII nerve rootlets were simultaneously recorded by using extracellular microelectrodes and suction electrodes, respectively. Roles of adenosine A1 receptors in modulation of respiratory rhythm were investigated by administration of the adenosine A1 receptor agonist R-phenylisopropyl-adenosine (R-PIA, 10 microM) and its specific antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 microM). DPCPX decreased the respiratory period (27.19%) and expiratory duration (28.27%) of biphasic E neurons and at the same time increased the peak discharge frequency (48.13%). By contrast, R-PIA produced opposite effects. On the other hand, the effects of DPCPX and R-PIA on the I neurons were similar to that on the biphasic E neurons except that R-PIA shortened the discharge duration of I neurons (34.12%) and decreased the peak discharge frequency (37.75%) in the middle phase of inspiration, but not in the initial and terminal phases. These results suggest that adenosine A1 receptors are involved in the phase-switching between expiration and inspiration by affecting biphasic E neurons. Activation of adenosine A1 receptors may modulate the inhibitory synaptic inputs from I neurons to biphasic E neurons.