| Title |
GSK3β inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion
|
|---|---|
| Published in |
Basic Research in Cardiology, April 2007
|
| DOI | 10.1007/s00395-007-0651-6 |
| Pubmed ID | |
| Authors |
E. R. Gross, A. K. Hsu, G. J. Gross |
| Abstract |
Both glycogen synthase kinase 3beta (GSK3beta) and the ATP-dependant potassium channel (K(ATP)) mediate opioid-induced cardioprotection (OIC). However, whether direct K(ATP) channel openers induce cardioprotection prior to reperfusion and their signaling cascade position with respect to GSK3beta inhibition is unknown. Therefore, we investigated the role of K(ATP) channel opening at reperfusion in OIC, and the interaction between the GSK signaling axis and K(ATP) channels in cardioprotection.Male Sprague-Dawley rats underwent 30 minutes ischemia with 2 hours of reperfusion and infarct size was determined. Rats given the nonselective opioid agonist, morphine (0.3 mg/kg), or the selective delta opioid agonist, BW373U86 (1.0 mg/kg), 5 minutes prior to reperfusion reduced infarct size (40.3+/-1.6*, 39.7+/-1.9* versus 60.0+/-1.1%, respectively, * P<0.001%). This protection was abrogated with prior administration of the putative sarcolemmal K(ATP) antagonist, HMR-1098 (6 mg/kg), or the putative mitochondrial K(ATP) antagonist, 5-HD (10 mg/kg). The putative sK(ATP) channel opener, P-1075 (1microg/kg) or the putative mK(ATP) channel opener, BMS-191095 (1 mg/kg) given 5 minutes prior to reperfusion also reduced infarct size (41.8+/-2.4*, 43.4+/-1.4*) and protection was abrogated by prior administration of the PI3k inhibitor wortmannin (60.0+/-1.7, 64.0+/-2.6%, respectively, * P<0.001). Cardioprotection afforded by the GSK inhibitor SB216763 (0.6 mg/kg) given 5 minutes prior to reperfusion was also partially blocked by either HMR or 5-HD and completely blocked when HMR and 5-HD were given in combination (40.8+/-1.6*, 50.4+/-1.6;; 49.4+/-1.7;, 61.6+/-1.6%, respectively, * or ; P<0.001). These data indicate that both the sK(ATP) and mK(ATP) channel are involved in acute OIC and the GSK signaling axis regulates cardioprotection via K(ATP) channel opening. |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 22% |
| Student > Bachelor | 3 | 17% |
| Student > Doctoral Student | 2 | 11% |
| Other | 2 | 11% |
| Student > Master | 2 | 11% |
| Other | 3 | 17% |
| Unknown | 2 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 39% |
| Biochemistry, Genetics and Molecular Biology | 3 | 17% |
| Chemistry | 2 | 11% |
| Nursing and Health Professions | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 3 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 September 2019.
All research outputs
#7,454,298
of 22,789,076 outputs
Outputs from Basic Research in Cardiology
#180
of 644 outputs
Outputs of similar age
#25,992
of 73,709 outputs
Outputs of similar age from Basic Research in Cardiology
#2
of 4 outputs
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