Nonexocytotic noradrenaline release from rat cardiac synaptosomal-mitochondrial fractions.
Nonexocytotic noradrenaline (NA) release was examined in rat cardiac synaptosomal-mitochondrial fractions prelabeled with [3H]NA (300 nM; 1 h at 37 degrees C). Ischemic conditions (1 mM iodoacetate + 2 mM NaCN; 15 min at 37 degrees C) evoked a Ca(2+)-independent release of [3H]NA from isolated synaptosomes, which represented 33.4% of total content, whereas the release evoked by 56 mM K+ was Ca2+ dependent and represented 5.8% of total content. Tyramine, phencyclidine (PCP), and rimcazole also caused important Ca(2+)-independent releases of [3H]NA (from 12 to 45% of total content) with median effective concentrations (EC50s) of 6.8, 182, and 41.8 microM, respectively. The release responses evoked by ischemic conditions, tyramine, PCP, and rimcazole were mimicked by the delta-receptor ligand, 1,3-ditolyl guanidine (DTG), and blocked by the uptake 1 inhibitor, desipramine (100 microM). The delta 1-receptors ligands, (+)-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) and (+)N-allylnormetazocine [(+)SKF-10047], were potent blockers of the release of [3H]NA evoked by ischemic conditions but not by PCP or rimcazole. These data indicate that ischemic conditions and PCP/delta 2-receptor ligands induce carrier-mediated NA efflux from cardiac sympathetic nerve terminals, whereas delta 1-receptor ligands produce marked inhibition of the ischemic response.
Dumont
M
M
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Roy
D
D
Lemaire
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010622:Phencyclidine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists; D013574:Synaptosomes / Q000378:metabolism*; D014439:Tyramine / Q000494:pharmacology
D014150:Antipsychotic Agents; D002227:Carbazoles; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D017465:Receptors, Opioid, delta; D003917:Dextrorphan; C034931:rimcazole; D010622:Phencyclidine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D014439:Tyramine