Adenosine A2A receptor-mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor-mediated effects in the rat vas deferens.
In the epididymal portion of rat vas deferens, facilitation of noradrenaline release mediated by adenosine A2A receptors, but not that mediated by beta2-adrenoceptors or by direct activation of adenylyl cyclase, was attenuated by blockade of alpha2-adrenoceptors and abolished by simultaneous blockade of alpha2-adrenoceptors, adenosine A1 and P2Y receptors. The adenosine A2A receptor-mediated facilitation was not changed by inhibitors of protein kinase A, protein kinase G or calmodulin kinase II but was prevented by inhibition of protein kinase C with chelerythrine or bisindolylmaleimide XI. Activation of protein kinase C with phorbol 12-myristate 13-acetate caused a facilitation of noradrenaline release that was abolished by bisindolylmaleimide XI and reduced by antagonists of alpha2-adrenoceptors, adenosine A1 and P2Y receptors. Activation of adenosine A2A receptors attenuated the inhibition of noradrenaline release mediated by the presynaptic inhibitory receptors. This effect was mimicked by phorbol 12-myristate 13-acetate and prevented by bisindolylmaleimide XI. It is concluded that adenosine A2A receptors facilitate noradrenaline release by a mechanism that involves a protein kinase C-mediated attenuation of effects mediated by presynaptic inhibitory receptors, namely alpha2-adrenoceptors, adenosine A1 and P2Y receptors.
Queiroz
Glória
G
Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Talaia
Carlos
C
Gonçalves
Jorge
J
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014649:Vas Deferens / Q000378:metabolism / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018341:Receptors, Adrenergic, alpha-2; D017661:Receptors, Presynaptic; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015016:Yohimbine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011493:Protein Kinase C; D000241:Adenosine; D009638:Norepinephrine