PMID- 9515033
OWN - NLM
STAT- MEDLINE
DCOM- 19980501
LR  - 20141120
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 30
IP  - 3
DP  - 1998 Mar
TI  - Relative importance of adenosine A1 and A3 receptors in mediating physiological 
      or pharmacological protection from ischemic myocardial injury in the rabbit 
      heart.
PG  - 579-85
AB  - Although ischemic preconditioning (IP) in several species can be 
      pharmacologically mimicked by selective adenosine A1 or A3 receptor agonists, it 
      is currently unclear which receptor subtype (A1 and/or A3) is physiologically 
      involved in mediating IP. To investigate this question, we determined (a) the 
      affinity of adenosine for rabbit adenosine A1 and A3 receptors, and (b) the 
      effects of selective rabbit A1 receptor blockade on IP and adenosine-mediated 
      cardioprotection in a rabbit Langendorff model of myocardial ischemia-reperfusion 
      injury. Adenosine was 19-fold selective for inhibition of 
      N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to recombinant rabbit 
      A1 v rabbit A3 receptors (A1 Ki: 28 nm; A3 Ki 532 nm). Buffer-perfused rabbit 
      hearts were exposed to 30 min regional ischemia and 120 min of reperfusion, and 
      infarct size was measured by tetrazolium staining and normalized for area-at-risk 
      (IA/AAR). Ischemic preconditioning (5 min global ischemia and 10 min reperfusion) 
      or adenosine (20 micro M, 5 min) perfusion reduced infarct size (IA/AAR) to 
      17+/-3 and 14+/-2%, respectively (controls: 59+/-2%). Ischemic preconditioning 
      and adenosine-mediated cardioprotection were completely blocked (57+/-2 and 
      61+/-4% IA/AAR, respectively) in the presence of a rabbit A1-selective 
      concentration (50 nm) of the antagonist BWA1433 (rabbit A1 Ki: 3 nm; A3 Ki; 746 n 
      m). Thus, whereas recent studies have demonstrated that selective A1 or A3 
      receptor agonists can both pharmacologically mimic IP, the results of the present 
      study suggest that the adenosine-mediated component of IP in the isolated rabbit 
      heart is preferentially mediated by adenosine A1 receptors, potentially due to 
      adenosine's selectivity for this receptor subtype.
CI  - Copyright 1998 Academic Press Limited
FAU - Hill, R J
AU  - Hill RJ
AD  - Department of Cardiovascular & Metabolic Diseases, Central Research Division, 
      Pfizer Inc., Groton, CT 06340, USA.
FAU - Oleynek, J J
AU  - Oleynek JJ
FAU - Magee, W
AU  - Magee W
FAU - Knight, D R
AU  - Knight DR
FAU - Tracey, W R
AU  - Tracey WR
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Purinergic P1 Receptor Agonists)
RN  - 0 (Purinergic P1 Receptor Antagonists)
RN  - 0 (Receptor, Adenosine A3)
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Xanthines)
RN  - 121496-66-0 (BW A1433)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/metabolism
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - In Vitro Techniques
MH  - Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Myocardial Reperfusion Injury/*metabolism/physiopathology/*prevention & control
MH  - Purinergic P1 Receptor Agonists
MH  - Purinergic P1 Receptor Antagonists
MH  - Rabbits
MH  - Receptor, Adenosine A3
MH  - Receptors, Purinergic P1/genetics/*metabolism
MH  - Transfection
MH  - Xanthines/pharmacology
EDAT- 1998/05/09 00:00
MHDA- 1998/05/09 00:01
CRDT- 1998/05/09 00:00
PHST- 1998/05/09 00:00 [pubmed]
PHST- 1998/05/09 00:01 [medline]
PHST- 1998/05/09 00:00 [entrez]
AID - S0022-2828(97)90621-0 [pii]
AID - 10.1006/jmcc.1997.0621 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 1998 Mar;30(3):579-85. doi: 10.1006/jmcc.1997.0621.