Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / pharmacology
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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In Vitro Techniques
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Male
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Neural Inhibition / physiology
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Norepinephrine / metabolism*
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Phenethylamines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Rats
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Rats, Wistar
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Receptor, Adenosine A2A
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Receptors, Adrenergic, alpha-2 / metabolism
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Receptors, Presynaptic / metabolism*
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Receptors, Purinergic P1 / metabolism*
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Receptors, Purinergic P2 / drug effects
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Receptors, Purinergic P2 / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Vas Deferens / metabolism
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Vas Deferens / physiology*
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Xanthines / pharmacology
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-Antagonists
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Enzyme Inhibitors
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Phenethylamines
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Receptor, Adenosine A2A
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Receptors, Adrenergic, alpha-2
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Receptors, Presynaptic
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Receptors, Purinergic P1
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Receptors, Purinergic P2
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Xanthines
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2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
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Yohimbine
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1,3-dipropyl-8-cyclopentylxanthine
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Protein Kinase C
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Adenosine
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Norepinephrine