Attempted antagonism of adenosine analogue induced depression of respiration.
Intracerebroventricular (ICV) administration of the stable adenosine analogue 2-chloroadenosine (2CA) to hyperoxic halothane-anesthetized rats produced a dose-dependent depression of respiration largely as a result of a decrease in tidal volume. Similar changes were noted after another adenosine analogue, phenylisopropyladenosine (PIA). Higher doses shifted the minute ventilation-PaCO2 curve to the right and decreased its slope. Bradycardia and hypotension were produced at doses which altered respiration. Neonatal destruction of brain serotonin or dopamine-containing nerve terminals did not alter the 2CA-induced respiratory depression. Naloxone significantly antagonized the respiratory and circulatory changes produced by 2CA though the changes produced by PIA were not significantly antagonized. Peripherally and intracerebroventricularly administered theophylline were largely ineffective in reversing the 2CA-induced respiratory depression. Thus, these data suggest that a major part of the respiratory depression produced by 2CA is due to indirect activation of opioid receptors. In contrast, very little of the respiratory depression after PIA is via mechanisms antagonized by naloxone. Thus, putative adenosine agonists appear to vary in the extent to which respiratory depression is provoked by interactions with opioid systems.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D001923:Brain Chemistry / Q000187:drug effects; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D015762:2-Chloroadenosine; D000628:Aminophylline; D010660:Phenylisopropyladenosine; D012701:Serotonin; D009270:Naloxone; D000241:Adenosine; D004298:Dopamine