PMID- 9530203
OWN - NLM
STAT- MEDLINE
DCOM- 19980414
LR  - 20190418
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 274
IP  - 3
DP  - 1998 Mar
TI  - TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of 
      Gi/o proteins and KATP channels.
PG  - H909-14
LID - 10.1152/ajpheart.1998.274.3.H909 [doi]
AB  - We have previously shown that delta (delta)-opioid receptors, most notably delta 
      1, are involved in the cardioprotective effect of ischemic preconditioning (PC) 
      in rats; however, the mechanism by which delta-opioid receptor-induced 
      cardioprotection is mediated remains unknown. Therefore, we hypothesized that 
      several of the known mediators of ischemic PC such as the ATP-sensitive potassium 
      (KATP) channel and Gi/o proteins are involved in the cardioprotective effect 
      produced by delta 1-opioid receptor activation. To address these possibilities, 
      anesthetized, open-chest Wistar rats were randomly assigned to five groups. 
      Control animals were subjected to 30 min of coronary artery occlusion and 2 h of 
      reperfusion. To demonstrate that stimulating delta 1-opioid receptors produces 
      cardioprotection, TAN-67, a new selective delta 1-agonist, was infused for 15 min 
      before the long occlusion and reperfusion periods. In addition, one group 
      received 7-benzylidenenaltrexone (BNTX), a selective delta 1-antagonist, before 
      TAN-67. To study the involvement of KATP channels or Gi/o proteins in delta 
      1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATP channel 
      antagonist, or pertussis toxin (PTX), an inhibitor of Gi/o proteins, was 
      administered before TAN-67. Infarct size (IS) as a percentage of the area at risk 
      (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR 
      as compared with control (56 +/- 2 to 27 +/- 5%, n = 5, P < 0.05). The 
      cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX 
      (51 +/- 3, 53 +/- 5, and 61 +/- 4%, n = 6 for each group, respectively). These 
      results are the first to suggest that stimulating the delta 1-opioid receptor 
      elicits a cardioprotective effect that is mediated via Gi/o proteins and KATP 
      channels in the intact rat heart.
FAU - Schultz J el-J
AU  - Schultz J el-J
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee 53226, USA.
FAU - Hsu, A K
AU  - Hsu AK
FAU - Nagase, H
AU  - Nagase H
FAU - Gross, G J
AU  - Gross GJ
LA  - eng
GR  - HL-08311/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Blood Glucose)
RN  - 0 (Potassium Channels)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (TAN 67)
RN  - 0 (Virulence Factors, Bordetella)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Blood Pressure
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors/*physiology
MH  - Heart Rate
MH  - Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Myocardial Infarction/drug therapy/*pathology
MH  - Pertussis Toxin
MH  - Potassium Channels/*physiology
MH  - Quinolines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, delta/*agonists
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1998/04/08 00:00
MHDA- 1998/04/08 00:01
CRDT- 1998/04/08 00:00
PHST- 1998/04/08 00:00 [pubmed]
PHST- 1998/04/08 00:01 [medline]
PHST- 1998/04/08 00:00 [entrez]
AID - 10.1152/ajpheart.1998.274.3.H909 [doi]
PST - ppublish
SO  - Am J Physiol. 1998 Mar;274(3):H909-14. doi: 10.1152/ajpheart.1998.274.3.H909.