Effect of tyramine on the production of interstitial adenosine during perfusion with adenosine 5'-monophosphate in rat hearts in vivo.

Abstract The present study was examined whether tyramine-released norepinephrine enhances the production of interstitial adenosine via stimulation of ecto-5′-nucleotidase (a key enzyme responsible for adenosine production) using microdialysis techniques in in situ rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and perfused in the presence of adenosine 5′-monophosphate. Tyramine (1 mM) increased the adenosine concentration measured in the presence of 100 μM adenosine 5′-monophosphate, an increase which was inhibited by antagonist of the α 1 -adrenoceptors (prazosin, 50 μM) or of a protein kinase C inhibitor (chlerythrine, 10 μM), and in reserpinized rats, tyramine failed to increase the adenosine 5′-monophosphate-primed dialysate adenosine concentration. norepinephrine is known to activate α 1 -adrenoceptors and protein kinase C. Taken together, the results demonstrate that tyramine-released norepinephrine activates both α 1 -adrenoceptors and protein kinase C, which increased ecto-5′-nucleotidase activity and augmented release of adenosine in rat hearts.