title: Activation of peripheral delta opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K+ channels.
abstract: The effects of the selective delta-1 (delta(1)) opioid receptor agonist, DPDPE, and the selective delta(2) opioid receptor agonist, DSLET, have been studied on the ventricular fibrillation threshold (VFT) in rats with an experimental post-infarction cardiosclerosis (CS). It has been found that CS induced a significant decrease in VFT. This CS-induced decrease in VFT was significantly reversed by intravenous administration of DPDPE (0.1 mg/kg) 10 min before VFT measurement. On the contrary, intravenous injection of DSLET (0.5 mg/kg) exacerbated the CS-induced cardiac electrical instability. Pretreatment with the selective delta opioid receptor antagonist, ICI 174,864 (0.5 mg/kg), completely abolished the changes in VFT produced by both DPDPE and DSLET. Previous administration of a nonselective peripherally acting opioid receptor antagonist, naloxone methiodide (5 mg/kg) also completely reversed the antifibrillatory action of DPDPE. Naloxone methiodide and ICI 174,864 alone had no effect on VFT. Pretreatment with the nonselective K(ATP) channel blocker, glibenclamide (0.3 mg/kg), or with the mitochondrial selective K(ATP) channel blocker, 5-hydroxydecanoic acid (5-HD, 5 mg/kg), completely abolished the DPDPE-induced increase in cardiac electrical stability. Glibenclamide and 5-HD alone had no effect on VFT. These results demonstrate that the delta opioid receptor plays an important role in the regulation of electrical stability in rats with post-infarction cardiosclerosis. We propose that peripheral delta(1) opioid receptor stimulation reverses CS-induced electrical instability via mitochondrial K(ATP) channels. On the contrary, delta(2) opioid receptor stimulation may exacerbate the CS-induced decrease in VFT. Further studies are necessary to determine the delta opioid receptor subtype which mediates the antifibrillatory effect of DPDPE and pro-fibrillatory effect of DSLET.
authors.affiliation: Laboratory of Experimental Cardiology, Institute of Cardiology, 634050 Tomsk, Russia.
authors.forename: L N
authors.initials: LN
authors.lastname: Maslov
authors.forename: Yu B
authors.initials: YB
authors.lastname: Lishmanov
authors.forename: N V
authors.initials: NV
authors.lastname: Solenkova
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
authors.forename: G B
authors.initials: GB
authors.lastname: Stefano
authors.forename: S W
authors.initials: SW
authors.lastname: Tam
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004336:Drug Antagonism; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*; D012598:Sclerosis; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D017465:Receptors, Opioid, delta; D009270:Naloxone; D004743:Enkephalin, Leucine; C052853:5-hydroxydecanoic acid; C041269:N-methylnaloxone; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D000255:Adenosine Triphosphate; D005905:Glyburide