Mironov, S. L., K. Langohr, and D. W. Richter. A1adenosine receptors modulate respiratory activity of the neonatal mouse via the cAMP-mediated signaling pathway. J. Neurophysiol. 81: 247–255, 1999. The effects of adenosine and its analogs on the function of the respiratory center were studied in the spontaneously active rhythmic slice of neonatal and juvenile mice (4–14 days old). Whole cell, spontaneous postsynaptic currents (sPSCs) and single channel KATPcurrents were recorded in inspiratory neurons of the pre-Bötzinger complex. Adenosine (50–600 μM) inhibited the respiratory rhythm. This was accompanied by increase in the activity of KATPchannels in cell-attached patches. The A1adenosine receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA, 0.3–2 μM), inhibited the respiratory rhythm, sPSCs, and enhanced activity of KATPchannels. The A1adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1–3 μM), showed opposite effects and occluded the CCPA actions. Agents specific for A2adenosine receptors (CGS 21860 and NECA, both applied at 1–10 μM) were without effect. Elevation of intracellular cAMP concentration ([cAMP]i) by 8-Br-cAMP (200–500 μM), forskolin (0.5–2 μM), or isobutylmethylxantine (IBMX, 30–90 μM) reinforced the rhythm, whereas NaF (100–800 μM) depressed it. The open probability of single KATPchannels in cell-attached patches decreased after application of forskolin and increased in the presence of NaF. [cAMP]ielevation reversed the effects of A1receptors both on the respiratory rhythm and KATPchannels. A1receptors and [cAMP]imodified the hypoxic respiratory response. In the presence of A1agonists the duration of hypoxic augmentation shortened, and depression of the respiratory rhythm occurred earlier. Elevation of [cAMP]iprolonged augmentation and delayed the development of the depression. We conclude that A1adenosine receptors modulate the respiratory rhythm via inhibition of intracellular cAMP production and concomitant activation of KATPchannels.