Aitchison, KA; Baxter, GF; Awan, MM; Smith, RM; Yellon, DM; 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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