title: Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic dopamine release.
abstract: Morphine and anandamide stimulate the release of nitric oxide (NO) in diverse tissues. The present study examines the consequences of this action on neurotransmitter release in ganglia from two invertebrates: ventral chain ganglia from the leech Hirudo medicinalis and the pedal ganglion from the mussel Mytilus edulis. In these ganglia, preloaded serotonin (5-HT) and dopamine (DA) can be released by 50 mM KCl. Anandamide, an endogenous cannabinoid substance, suppresses the potassium-stimulated release of [3H]DA (80%), but not 5-HT, in a concentration-dependent manner, from the neural tissues of both. The effect of anandamide can be antagonized by pre-exposing the neural tissues of both animals to SR 141716A, a potent cannabinoid receptor antagonist. Prior treatment of the ganglia with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, significantly diminishes the inhibitory effect of anandamide. Morphine also inhibits [3H]DA release in a naloxone- and L-NAME-sensitive manner. Anandamide and morphine act through separate mechanisms since the respective antagonists show no cross-reactivity. The NO donor, SNAP, depressed the potassium-stimulated release of preloaded [3H]DA, but not 5-HT, in the neural tissues of both animals. D-Ala2-Met5 enkephalinamide (DAMA) also inhibited the potassium-stimulated release of [3H]DA in a naloxone-sensitive process. However, the effect of DAMA was seen in the presence of L-NAME (10(-4) M), indicating that the opioid peptide inhibition of the presynaptic release of DA is not coupled to NO. We postulate that cannabinoids and their endogenous effectors play a prominent role in the regulation of catecholamine release in invertebrates via NO release as is the case for opiate alkaloids.
authors.affiliation: Multidisciplinary Center for the Study of Aging, Neuroscience Research Institute, State University of New York, College at Old Westbury, 11568, USA. stefanog@surg.som.sunysb.edu
authors.forename: G B
authors.initials: GB
authors.lastname: Stefano
authors.forename: B
authors.initials: B
authors.lastname: Salzet
authors.forename: C M
authors.initials: CM
authors.lastname: Rialas
authors.forename: M
authors.initials: M
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: Kustka
authors.forename: K
authors.initials: K
authors.lastname: Neenan
authors.forename: S
authors.initials: S
authors.lastname: Pryor
authors.forename: M
authors.initials: M
authors.lastname: Salzet
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D063388:Endocannabinoids; D017952:Ganglia, Invertebrate / Q000187:drug effects; D007865:Leeches; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D053284:Polyunsaturated Alkamides; D017729:Presynaptic Terminals / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D009569:Nitric Oxide; D009020:Morphine; C078814:anandamide; D004298:Dopamine