Effects of the neoclerodane Hardwickiic acid on the presynaptic opioid receptors which modulate noradrenaline and dopamine release in mouse central nervous system.
We have comparatively investigated the effects of Hardwickiic acid and Salvinorin A on the K(+)-evoked overflow of [(3)H]noradrenaline ([(3)H]NA) and [(3)H]dopamine ([(3)H]DA) from mouse hippocampal and striatal nerve terminals, respectively. The K(+)-evoked overflow of [(3)H]DA was inhibited in presence of Salvinorin A (100 nM) but not in presence of Hardwickiic acid (100 nM). Hardwickiic acid (100 nM) mimicked Salvinorin A (100 nM) in facilitating K(+)-evoked hippocampal [(3)H]NA overflow and the two compounds were almost equipotent. Facilitation of [(3)H]NA overflow caused by 100 nM Hardwickiic acid was prevented by the κ-opioid receptor (KOR) antagonist norbinaltorphimine (norBNI, 100 nM) and by the selective δ-opioid receptor (DOR) antagonist naltrindole (100 nM), but was not altered by 100 nM D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), a selective μ-opioid receptor (MOR) antagonist. We conclude that Hardwickiic acid modulates hippocampal [(3)H]NA overflow evoked by a mild depolarizing stimulus by acting at presynaptic opioid receptor subtypes.
Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Italy.
Anna
A
Pittaluga
Guendalina
G
Olivero
Silvia
S
Di Prisco
Elisa
E
Merega
Angela
A
Bisio
Giovanni
G
Romussi
Massimo
M
Grilli
Mario
M
Marchi
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects*
D004224:Diterpenes; D011957:Receptors, Opioid; C074343:hardwickic acid; D004298:Dopamine; D009638:Norepinephrine