Faculty Collaboration Database

ERK and p38 MAP kinase activation are components of opioid-induced delayed cardioprotection. Basic Res Cardiol 2001 Apr;96(2):136-42

Date

05/01/2001

Pubmed ID

11327331

DOI

10.1007/s003950170063

Scopus ID

2-s2.0-0035074421 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

Opioids have been previously shown to confer acute and delayed cardioprotection against a prolonged ischemic insult. We have extensively characterized the signal transduction pathway mediating acute cardioprotection and have suggested a role for extracellular signal regulated kinase (ERK) in this cardioprotection. Therefore, we attempted to determine a role for ERK and the stress activated MAP kinase, p38, in opioid-induced delayed cardioprotection by using selective inhibitors of these pathways. All rats were subjected to 30 min of ischemia and 2 h of reperfusion (I/R). Control animals, injected with saline 48 h prior to I/R, had an infarct size/area at risk (IS/AAR) of 61.6 +/- 1.6.48-h pretreatment with TAN-67 (30 mg/kg), a delta1-opioid receptor agonist, maximally reduced IS/AAR (31.2 +/- 6.5). The involvement of ERK was examined with PD 098059, a selective pharmacological antagonist which inhibits the upstream kinase, MEK-1, that phosphorylates and activates ERK. PD 098059 (0.3 mg/kg) did not alter IS/AAR when administered alone (60.7 +/- 4.9). However, PD 098059 (0.3 mg/kg) administration 30 min prior to TAN-67 (30 mg/kg) completely abolished cardioprotection (61.0 +/- 7.6). The selective p38 inhibitor, SB 203580 (1.0 mg/kg), had no effect on IS/AAR in the absence of TAN-67 (53.1 +/- 2.3). Additionally, SB 203580 (1.0 mg/kg) when administered prior to TAN-67 (30 mg/kg) partially abolished cardioprotection (51.3 +/- 6.4). These results suggest that both ERK and p38 are integral components of opioid-induced delayed cardioprotection and may act via parallel pathways.

Author List

Fryer RM, Hsu AK, Gross GJ

MESH terms used to index this publication - Major topics in bold

Analgesics
Animals
Blood Pressure
Enzyme Activation
Enzyme Inhibitors
Flavonoids
Heart Rate
Imidazoles
Ischemic Preconditioning, Myocardial
MAP Kinase Signaling System
Male
Mitogen-Activated Protein Kinases
Myocardial Ischemia
Myocardium
Pyridines
Quinolines
Rats
Rats, Wistar
Receptors, Opioid
p38 Mitogen-Activated Protein Kinases