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Opioid receptor stimulation acts as mediator of protection in ischaemic preconditioning.
- Source :
-
Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners [Cardiovasc J S Afr] 2001 Feb-Mar; Vol. 12 (1), pp. 8-16. - Publication Year :
- 2001
-
Abstract
- Involvement of the opioid receptors in preconditioning-induced protection has recently been described. The aims of this study were to establish whether: (i) opioid receptor stimulation acts as a trigger ( during the preconditioning protocol) or as a mediator ( during sustained ischaemia) of cardioprotection using either morphine or [D-ala(2), D-leu(5)] enkephalin (DADLE), a synthetic delta-opioid receptor agonist; ( ii) the beneficial effects of DADLE are protein kinase C ( PKC) -mediated; and (iii) inhibitory 'cross-talk' occurs between the beta-adrenergic and phosphatidylinositol pathways activated by release of endogenous catecholamines and opioids respectively during sustained ischaemia. The isolated, perfused working rat heart, subjected to 25 minutes' global ischaemia and 30 minutes' reperfusion, was used as the experimental model. The results showed that delta-opioid receptor stimulation with DADLE (10(-8) M), when administered for 3 x 5 minutes, had no effect, while when given 10 minutes before sustained ischaemia the drug significantly improved functional recovery during reperfusion. This indicates that opioid receptor stimulation acts as a mediator rather than a trigger in the protection elicited. Morphine ( 3 x 10(-7)) when administered in the same manner was without effect. Opioid receptor stimulation caused a marked reduction in the beta -adrenergic response to isoproterenol, indicating inhibitory cross-talk between the phosphatidyl-inositol and beta-adrenergic signal transduction pathways. However, reduction of the beta-adrenergic response to ischaemia does not appear to be the mechanism of opioid-induced protection, as indicated by 3',5' -cyclic adenosine monophosphate (cAMP) levels at the end of 25 minutes' global ischaemia. Opioid receptor-mediated protection against ischaemic damage is PKC-dependent, since DADLE-induced protection could be abolished by the inhibitor chelerythrine.
- Subjects :
- Adrenergic beta-Agonists administration & dosage
Alkaloids
Animals
Bacterial Proteins drug effects
Benzophenanthridines
Blood Pressure drug effects
Coronary Vessels drug effects
Coronary Vessels physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Enkephalin, Leucine-2-Alanine administration & dosage
Enkephalin, Leucine-2-Alanine agonists
Enkephalin, Leucine-2-Alanine antagonists & inhibitors
Enzyme Inhibitors administration & dosage
Heart drug effects
Heart Rate drug effects
Hemolysin Proteins
Isoproterenol administration & dosage
Male
Morphine administration & dosage
Morphine agonists
Naloxone administration & dosage
Naloxone antagonists & inhibitors
Narcotic Antagonists administration & dosage
Phenanthridines administration & dosage
Phenanthridines antagonists & inhibitors
Phosphotransferases (Alcohol Group Acceptor) drug effects
Protein Kinase C drug effects
Rats
Rats, Wistar
Recovery of Function drug effects
Regional Blood Flow drug effects
Reperfusion methods
Stimulation, Chemical
Ischemic Preconditioning, Myocardial
Receptors, Opioid administration & dosage
Receptors, Opioid agonists
Subjects
Details
- Language :
- English
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners
- Publication Type :
- Academic Journal
- Accession number :
- 11447487