An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells.
We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats. The effect of A2B adenosine and D2 dopamine agonists and antagonists applied alone or in combination were studied on basal (20%O2) and hypoxia (10%O2)-evoked release of CA and cAMP content of CB. We have found that adenosine A2 agonists and D2 antagonists dose-dependently increased basal and evoked release CA from the CB while A2 antagonists and D2 agonists had an inhibitory action. The existence of A2B-D2 receptor interaction was established because the inhibitory action of A2 antagonists was abolished by D2 antagonists, and the stimulatory action of A2 agonists was abolished by D2 agonists. Further, A2 agonists increased and D2 agonist decreased cAMP content in the CB; their co-application eliminated the response. The present results provide direct pharmacological evidence that an antagonistic interaction between A2B adenosine and D2 dopamine receptors exist in rat CB and would explain the dopamine-adenosine interactions on ventilation previously observed.
Conde
Silvia V
SV
Department of Pharmacology, Faculty of Medical Sciences, New University of Lisbon, Portugal. silvia.conde@fcm.unl.pt
Gonzalez
Constancio
C
Batuca
Joana R
JR
Monteiro
Emilia C
EC
Obeso
Ana
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002344:Carotid Body / Q000166:cytology*; D002395:Catecholamines / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D010100:Oxygen / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology
D000081:Acetamides; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D002395:Catecholamines; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; C423842:N-(4-cyanophenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy)acetamide; D010627:Phenethylamines; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D043704:Receptor, Adenosine A2B; D017448:Receptors, Dopamine D2; D014665:Vasodilator Agents; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D000242:Cyclic AMP; D000241:Adenosine; D010100:Oxygen; D015056:1-Methyl-3-isobutylxanthine