Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic dopamine release.
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.
Stefano
G B
GB
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
Salzet
B
B
Rialas
C M
CM
Pope
M
M
Kustka
A
A
Neenan
K
K
Pryor
S
S
Salzet
M
M
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*
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D009569:Nitric Oxide; D009020:Morphine; C078814:anandamide; D004298:Dopamine