G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a Mu opioid and an adenosine A1 receptor agonist

D. Tanase, W. A. Martin, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Study Objectives: Opioids delivered to the ports 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 Gj/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. Design: Activation of G proteins was assessed autoradiographicalty by agonist stimulation of [35S]GTPγS 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. Setting: N/A Patients or Participants: N/A Measurements and 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]GTPγS binding that was blocked by DPCPX. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalSleep
Volume24
Issue number1
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

Fingerprint

Adenosine A1 Receptor Agonists
GTP-Binding Proteins
Opioid Analgesics
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Brain Stem
Adenosine A1 Receptors
Therapeutics
Nociception
REM Sleep
Adenosine
Sleep
Pedunculopontine Tegmental Nucleus
Adenosine A1 Receptor Antagonists
Periaqueductal Gray
mu Opioid Receptor

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

Cite this

G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a Mu opioid and an adenosine A1 receptor agonist. / Tanase, D.; Martin, W. A.; Baghdoyan, Helen; Lydic, Ralph.

In: Sleep, Vol. 24, No. 1, 01.02.2001, p. 52-62.

Research output: Contribution to journalArticle

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abstract = "Study Objectives: Opioids delivered to the ports 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 Gj/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. Design: Activation of G proteins was assessed autoradiographicalty by agonist stimulation of [35S]GTPγS 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. Setting: N/A Patients or Participants: N/A Measurements and 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]GTPγS binding that was blocked by DPCPX. Conclusion: 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.",
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