Influence of diazepam, alpidem, zolpidem and zopiclone, on the response to adenosine of the guinea pig isolated trachea.
It has been reported that dipyridamole and some benzodiazepines potentiate the responses to adenosine in peripheral organs and in particular in the guinea pig isolated atria or trachea by inhibition of adenosine uptake and/or metabolism. In this study, we have examined the sensitization of guinea pig isolated trachea to relaxant responses to adenosine produced by dipyridamole, diazepam and 3 compounds chemically unrelated to benzodiazepines but which display selective agonistic activity towards the central (zolpidem and zopiclone) or peripheral (alpidem) type benzodiazpine receptors. In preparations under spontaneous tone and in the absence of adenosine, dipyridamole (10(-5) M) and diazepam (10(-5)-10(-4) M), alpidem (3 x 10(-6) M-10(-5) M) and zopiclone (10(-6)-10(-4) M) induced a relaxation of the airway smooth muscle. In addition, dazepam (10(-4) M) attenuated the phasic response to histamine (10(-5) M). Dipyridamole (10(-5) M) and diazepam (10(-4) M) respectively produced a 56.2 and 32.4-fold potentiation of adenosine relaxant effects. Alpidem (10(-6)-10(-5) M), zolpidem (10(-6)-10(-4) M) and zopiclone (10(-6)-10(-4) M) were without any significant effect on the adenosine concentration-response curves. Moreover, alpidem, zolpidem, and zopiclone did not modify the 2-chloroadenosine dose-response curves nor the diazepam induced sensitization of adenosine-induced relaxation. In conclusion, adenosine sensitization of the guinea pig isolated trachea caused by diazepam might involve a peripheral benzodiazpine receptor subtype coupled to a nucleoside transporter system which is different from those recognized by compounds derived from the imidazopyridine series.
Departement of Pharmacology, Faculty of Medicine, Paris, France.
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Candenas
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Devillier
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Advenier
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011725:Pyridines; D011963:Receptors, GABA-A; D015762:2-Chloroadenosine; D004176:Dipyridamole; D000077334:Zolpidem; D006632:Histamine; C052036:alpidem; D000241:Adenosine; D003975:Diazepam