Effects of lysophosphatidylcholine on the production of interstitial adenosine via protein kinase C-mediated activation of ecto-5'-nucleotidase.
1. Adenosine plays a crucial role in the evolution of ischemic preconditioning. With the use of microdialysis techniques in in situ rat hearts, we assessed the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production), and examined the effects of lysophosphatidylcholine (LPC) on the production of interstitial adenosine. 2. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP, 100 microM). With this system, the dialysate adenosine originates from the dephosphorylation of AMP, catalyzed by endogenous ecto-5'-nucleotidase. The level of dialysate adenosine is a measure of the ecto-5'-nucleotidase activity in vivo. 3. LPC at concentrations of 25 and 50 microM significantly increased the level of dialysate adenosine to 122.7+/-4.3% (n=4, P<0.05) and 158.6+/-7.2% (n=5, P<0.05) of the control, respectively. Chelerythrine (200 microM), a protein kinase C (PKC) inhibitor, completely abolished the increase of dialysate adenosine afforded by LPC (50 microM) (n=5). 4. These data provide the first evidence that LPC does increase the concentration of interstitial adenosine in rat hearts in situ, through the PKC-mediated activation of endogenous ecto-5'-nucleotidase.
Sato
T
T
Department of Physiology, Oita Medical University, Hasama, Japan.
Obata
T
T
Yamanaka
Y
Y
Arita
M
M
D000241:Adenosine / Q000032:analysis / Q000096:biosynthesis*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D005260:Female; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D008244:Lysophosphatidylcholines; D011493:Protein Kinase C; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D000241:Adenosine