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

J Neurochem. 2003 May;85(3):740-8. doi: 10.1046/j.1471-4159.2003.01715.x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Male
  • Neural Inhibition / physiology
  • Norepinephrine / metabolism*
  • Phenethylamines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A2A
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Presynaptic / metabolism*
  • Receptors, Purinergic P1 / metabolism*
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Vas Deferens / metabolism
  • Vas Deferens / physiology*
  • Xanthines / pharmacology
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Enzyme Inhibitors
  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptor, Adenosine A2A
  • Receptors, Adrenergic, alpha-2
  • Receptors, Presynaptic
  • Receptors, Purinergic P1
  • Receptors, Purinergic P2
  • Xanthines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Yohimbine
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Protein Kinase C
  • Adenosine
  • Norepinephrine