The A(2B)-D(2) receptor interaction that controls carotid body catecholamines release locates between the last two steps of hypoxic transduction cascade.
We have recently demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A(2B) receptors. Here, we have investigated the hypothesis that this control is exerted via an interaction between adenosine A(2B) and dopamine D(2) receptors present in chemoreceptor cells and if it is, the location of this interaction on the CB hypoxic transduction cascade. Experiments were performed in vitro in CB from 3 months rats. The effect of adenosine A(2B) and dopamine D(2) receptor agonists applied alone or conjunctly, was studied on the basal and evoked release (10% O(2) and ionomycin) of CA from CB. We have observed that the inhibitory action of propylnorapomorphine, a D(2) selective agonist, on the normoxic and 10%O(2)-evoked release of CA was abolished by NECA, an A(2) agonist, meaning that an interaction between the D(2) and A(2B) receptors controls the release of CA from CB. Further, propylnorapomorphine inhibits the release of CA evoked by ionomycin, being this effect totally reversed by NECA. The present results provide direct pharmacological evidence that A(2B) and D(2) receptors interact to modulate the release of CA from rat CB between the steps of Ca(2+) entry and increase in intracellular free Ca(2+), and the activation of exocytosis and neurotransmitter release, of the stimulus-secretion coupling process.
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Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Facultad de Medicina. Instituto de Biología y Genética Molecular, 47005 Valladolid, Spain. silvia.conde@fcm.unl.pt
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Monteiro
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Gonzalez
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D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction
D002395:Catecholamines; D018491:Dopamine Agonists; D043704:Receptor, Adenosine A2B; D017448:Receptors, Dopamine D2; D019830:Adenosine-5'-(N-ethylcarboxamide); D015759:Ionomycin; C009074:N-n-propylnorapomorphine; D001058:Apomorphine