title: G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a mu opioid and an adenosine A1 receptor agonist.
abstract: OBJECTIVE
  Opioids delivered to the pons inhibit REM sleep, whereas pontine administration of adenosine enhances REM sleep. In other brain areas opioids and adenosine interact to produce antinociception. Adenosine A1 receptors and mu opioid receptors each activate Gi/Go proteins. This study tested the hypothesis that combined treatment with the adenosine A1 receptor agonist SPA and the mu opioid agonist DAMGO would enhance G protein activation to a greater level than produced by either agonist alone. G protein activation was quantified in seven brainstem regions regulating sleep and nociception. This study also tested the hypothesis that G protein activation caused by SPA would be concentration dependent and blocked by the adenosine A1 receptor antagonist DPCPX.
  
  
  METHODS
  Activation of G proteins was assessed autoradiographically by agonist stimulation of [35S]GTPgammaS 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 periaqueductal gray, and laterodorsal and pedunculopontine tegmental nuclei.
  
  
  METHODS
  N/A.
  
  
  METHODS
  N/A.
  
  
  RESULTS
  Combined treatment with SPA and DAMGO caused a partially additive increase in G protein activation that was significantly (p<0.01) greater than G protein activation caused by either agonist alone. Treatment with SPA alone caused a concentration dependent (p<0.001) increase in [35S]GTPgammaS binding that was blocked by DPCPX.
  
  
  CONCLUSIONS
  Agonist activation of adenosine A1 receptors stimulates G proteins in brainstem nuclei regulating sleep and nociception. In these same nuclei, G protein activation by combined treatment with DAMGO and SPA was partially additive, suggesting that mu opioid and adenosine A1 receptors activate some common G protein pools.
authors.affiliation: Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tanase
authors.forename: W A
authors.initials: WA
authors.lastname: Martin
authors.forename: H A
authors.initials: HA
authors.lastname: Baghdoyan
authors.forename: R
authors.initials: R
authors.lastname: Lydic
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D004359:Drug Therapy, Combination; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects / Q000378:metabolism; D012895:Sleep, REM / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D018047:Receptors, Purinergic P1; D014970:Xanthines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019204:GTP-Binding Proteins