δ-Opioid receptor-induced late preconditioning is mediated by cyclooxygenase-2 in conscious rabbits

2002 ◽  
Vol 283 (5) ◽  
pp. H1943-H1957 ◽  
Author(s):  
Eitaro Kodani ◽  
Yu-Ting Xuan ◽  
Ken Shinmura ◽  
Hitoshi Takano ◽  
Xian-Liang Tang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Myocardial Stunning ◽  
Cyclooxygenase 2 ◽  
Late Preconditioning ◽  
Opioid Receptor Agonist ◽  
Cox 2 ◽  
Conscious Rabbits ◽  
Δ Opioid Receptor ◽  
Cox 2 Inhibitors

Although activation of δ-opioid receptors is known to induce both early and late preconditioning (PC) against myocardial infarction, the mechanisms for this salubrious effect are unclear. Furthermore, it is unknown whether δ-opioid receptors can also induce late PC against myocardial stunning. By using conscious rabbits ( n = 120) in this study, we found that the δ-opioid receptor agonist (±)-4-{(α- R*)-α-[(2 S*,5 R*)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl}- N, N-diethylbenzamide (BW-373U86) induced late PC against myocardial stunning 24 h after treatment and that this effect was abolished by the selective cyclooxygenase-2 (COX-2) inhibitors N-[2-(cyclohexyloxy)4-nitrophenyl]methanesulfonamide (NS-398) and celecoxib. This protective effect was also abrogated by the selective δ1-opioid receptor antagonist 7-benzylidenenaltrexone, indicating that the δ1-opioid receptor is necessary for BW-373U86-induced late PC. BW-373U86 did not induce early PC against stunning. In addition, BW-373U86 induced late PC against infarction, which was blocked by NS-398. At 24 h after BW-373U86 administration, myocardial COX-2 protein expression and PGE2 and 6-keto-PGF1α levels were significantly increased. These results demonstrate that activation of δ-opioid receptors induces late PC against both stunning and infarction via a COX-2-dependent mechanism.

scholarly journals TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/oproteins and KATPchannels

1998 ◽  
Vol 274 (3) ◽  
pp. H909-H914 ◽  
Author(s):  
Jo El J. Schultz ◽  
Anna K. Hsu ◽  
Hiroshi Nagase ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Cardioprotective Effect ◽  
Area At Risk ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

We have previously shown that delta (δ)-opioid receptors, most notably δ1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which δ-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/oproteins are involved in the cardioprotective effect produced by δ1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating δ1-opioid receptors produces cardioprotection, TAN-67, a new selective δ1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective δ1-antagonist, before TAN-67. To study the involvement of KATPchannels or Gi/oproteins in δ1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATPchannel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/oproteins, was administered before TAN-67. Infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR as compared with control (56 ± 2 to 27 ± 5%, n = 5, P < 0.05). The cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX (51 ± 3, 53 ± 5, and 61 ± 4%, n = 6 for each group, respectively). These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/oproteins and KATPchannels in the intact rat heart.

Properties of TAN-67, a nonpeptide δ-opioid receptor agonist, at cloned human δ-and μ-opioid receptors

1995 ◽  
Vol 291 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Richard J. Knapp ◽  
Robert Landsman ◽  
Sue Waite ◽  
Ewa Malatynska ◽  
Eva Varga ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Agonist ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor ◽  
Μ Opioid Receptors

scholarly journals The δ Opioid Receptor Agonist SNC80 Selectively Activates Heteromeric μ–δ Opioid Receptors

2012 ◽  
Vol 3 (7) ◽  
pp. 505-509 ◽  
Author(s):  
Matthew D. Metcalf ◽  
Ajay S. Yekkirala ◽  
Michael D. Powers ◽  
Kelley F. Kitto ◽  
Carolyn A. Fairbanks ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Agonist ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

Cardiovascular Properties of Metkephamid, a δ Opioid Receptor Agonist, in Man

1985 ◽  
Vol 68 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Fabrizio Pasanisi ◽  
Lesley Sloan ◽  
Peter C. Rubin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Supine Position ◽  
Receptor Agonist ◽  
Noradrenaline Concentration ◽  
Opioid Receptor Agonist ◽  
Head Up Tilt ◽  
Δ Opioid Receptor

1. Opioid receptors exist in at least three forms: μ, δ and κ. Agonists at μ receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective δ opioid receptor agonist. 2. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70° 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo. 3. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect. 4. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration. 5. We conclude that δ as well as μ opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with μ receptor agonists, suggesting a possible role of δ opioid receptors in cholinergic activity.

The K+-evoked release of [3H]acetylcholine from slices of rat globus pallidus: modulation by δ-opioid receptors

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Globus Pallidus ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Release Of Acetylcholine ◽  
Δ Opioid Receptor ◽  
Tritium Release

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.

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