Aitchison, KA and Baxter, GF and Awan, MM and Smith, RM and Yellon, DM and Opie, LH (2000) Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning. BASIC RES CARDIOL , 95 (1) 1 - 10.
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delta-Opioid receptors are known to participate in the protection found following ischemic preconditioning (IPC), but the role of kappa-receptors in IPC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischemia) substantially reduced infarct size. Pharmacological PC with the delta-agonist DADLE (10 nmol/L) had similar protective effects. However, higher dose DADLE (1 mu mol/L) had a less beneficial effect, and in conjunction with the delta-antagonist naltrindole unexpectedly increased infarct size (61.5 +/- 2.0 %, p<0.05 v 45.9 +/- 2.4 % in controls) suggesting a non-delta effect. The universal kappa-opioid agonist bremazocine (30 nmol/L) increased infarct size (61.3 +/- 1.6 %, p<0.05 v controls), an effect abrogated by the selective kappa(1)-antagonist nor-binaltorphimine (BNI).Since opiates are known to have anti-adrenergic effects, which hypothetically may help to mediate LPC, cyclic AMP levels were measured in DADLE and in bremazocine-treated hearts. Decreased levels of cyclic AMP at the start of the regional ischemic period were found in low dose DADLE hearts (0.485 +/- 0/020, n = 8, vs controls, 0.654 +/- 0.025 nmol/g wet weight, p<0.001), but not in high dose DADLE nor in bremazocine treated hearts.Thus, in the isolated rat heart kappa(1)-opioid receptor activation exacerbates infarct size through an as yet unknown mechanism, suggesting that there could be an "anti-preconditioned state". In contrast, delta-activity mediates protection which may be associated with a reduction of tissue cyclic AMP levels.
|Title:||Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning|
|Keywords:||delta opioid receptor, kappa opioid receptor, preconditioning, regional ischemia, infarct size, PROTEIN-KINASE-C, MYOCARDIAL-ISCHEMIA, REPERFUSION, AGONISTS, ANTAGONISTS, PEPTIDE, STIMULATION, INVOLVEMENT, INHIBITORS, PROTECTION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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