G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a mu opioid and an adenosine A(1) receptor agonist

Study Objectives: Opioids delivered to the pens inhibit REM sleep, whereas pontine administration of adenosine enhances REM sleep. In other brain area s opioids and adenosine interact to produce antinociception. Adenosine A(1) receptors and mu opioid receptors each activate G(i)/G(o) proteins. This s tudy tested the hypothesis that combined treatment with the adenosine A(1) receptor agonist SPA and the mu opioid agonist DAMGO would enhance G protei n activation to a greater level than produced by either agonist alone. G pr otein activation was quantified in seven brainstem regions regulating sleep and nociception. This study also tested the hypothesis that G protein acti vation caused by SPA would be concentration dependent and blocked by the ad enosine A(1) receptor antagonist DPCPX. Design: Activation of G proteins was assessed autoradiographically by agoni st stimulation of [S-35]GTP gammaS binding in slide-mounted sections of rat brainstem. G protein activation was quantified in nCi/g tissue for pontine reticular formation, dorsal raphe, ventrolateral and dorsomedial peri-aque ductal gray, and laterodorsal and pedunculopontine tegmental nuclei. Setting: N/A Patients or Participants: N/A Measurements and Results: Combined treatment with SPA and DAMGO caused a pa rtially additive increase in G protein activation that was significantly (p <0.01) greater than G protein activation caused by either agonist alone. Tr eatment with SPA alone caused a concentration dependent (p<0.001) increase in [S-35]GTP gammaS binding that was blocked by DPCPX. Conclusion: Agonist activation of adenosine A(1) receptors stimulates G pro teins in brainstem nuclei regulating sleep and nociception. In these same n uclei, G protein activation by combined treatment with DAMGO and SPA was pa rtially additive, suggesting that mu opioid and adenosine A(1) receptors ac tivate some common G protein pools.