期刊
NEUROPHARMACOLOGY
卷 57, 期 5-6, 页码 523-530出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.07.023
关键词
Salvinorin A; Presynaptic kappa Opioid receptor subtypes; Dopamine release; Noradrenaline release; Serotonin release; Synaptosomes
资金
- Italian MIUR(Ministero dell'Istruzione, dell'Universita e della Ricerca)
- Compagnia di San Paolo, Turin, Italy [2005054943004]
- University of Genoa 'Progetto Ricerca Ateneo
- ALCOTRA (Alpi Latine Cooperazione Transfrontaliera)
We investigated the effects of salvinorin A on the basal and the 12 mM K+-evoked release of preloaded [H-3]noradenaline ([H-3]NA) and [H-3]serotonin ([H-3]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12 mM K+-evoked release of preloaded [H-3]dopamine ([H-3]DA) from mouse striatal and prefrontal cortex (PFc) synaptosomes. Salvinorin A (0.1-1000 nM) failed to affect the basal release of amines, but inhibited the 12 mM K+-evoked, Ca2+-dependent, exocytotic-like release of [H-3]5-HT and [H-3]DA. At the same concentration, sal(3)Hinorin A facilitated the 12 mM K+-evoked, Ca2+-dependent, exocytotic-like release of [H-3]NA. These effects could not be observed in pertussis toxin (PTx) entrapped synaptosomes. The broad spectrum K-Opioid receptor (KOR) antagonist norbinaltorphimine (norBNI, 1-100 nM) antagonized the inhibition of [H-3]5-HT and [H-3]DA exocytosis as well as the facilitation of [H-3]NA overflow induced by 100 nM salvinorin A. The KOR agonist U69593 (1-100 nM) mimicked salvinorin A in inhibiting [H-3]5-HT and of [H-3]DA exocytosis, its effect being prevented by norBNI, but leaving unchanged the K+-evoked release of [H-3]NA. The effects of Salvinorin A on neurotransmitter exocytosis were not prevented by the selective mu opioid (MOR) receptor antagonist CTAP (10-100 nM), whereas facilitation of [H-3]NA exocytosis, but not inhibition of [H-3]5-HT and [H-3]DA K+-evoked release, was counteracted by the delta opioid receptor (DOR) antagonist naltrindole (1-100 nM). We conclude that salvinorin A presynaptically modulates central NA, 5-HT, and DA exocytosis evoked by a mild depolarizing stimulus by acting at presynaptic opioid receptors having different pharmacological profiles. (C) 2009 Elsevier Ltd. All rights reserved.
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