MORPHINE-STIMULATED AND ANANDAMIDE-STIMULATED NITRIC-OXIDE PRODUCTIONINHIBITS PRESYNAPTIC DOPAMINE RELEASE

Morphine and anandamide stimulate the release of nitric oxide (NO) in diverse tissues. The present study examines the consequences of this a ction on neurotransmitter release in ganglia from two invertebrates: v entral chain ganglia from the leech Hirudo medicinalis and the pedal g anglion from the mussel Mytilus edulis. In these ganglia, preloaded se rotonin (5-HT) and dopamine (DA) can be released by 50 mM KCI. Anandam ide, an endogenous cannabinoid substance, suppresses the potassium-sti mulated release of [H-3]DA (80%), but not 5-HT, in a concentration-dep endent manner, from the neural tissues of both. The effect of anandami de can be antagonized by pre-exposing the neural tissues of both anima ls to SR 141716A, a potent cannabinoid receptor antagonist. Prior trea tment of the ganglia with N-omega-nitro-L-arginine methyl ester (L-NAM E), a nitric oxide synthase inhibitor, significantly diminishes the in hibitory effect of anandamide. Morphine also inhibits [H-3]DA release in a naloxone- and L-NAME-sensitive manner. Anandamide and morphine ac t through separate mechanisms since the respective antagonists show no cross-reactivity. The NO donor, SNAP, depressed the potassium-stimula ted release of preloaded [H-3]DA, but not 5-HT, in the neural tissues of both animals. D-Ala(2)-Met(5) enkephalinamide (DAMA) also inhibited the potassium-stimulated release of [H-3]DA in a naloxone-sensitive p rocess, However, the effect of DAMA was seen in the presence of L-NAME (10(-4) M), indicating that the opioid peptide inhibition of the pres ynaptic release of DA is not coupled to NO. We postulate that cannabin oids and their endogenous effecters play a prominent role in the regul ation of catecholamine release in invertebrates via NO release as is t he case for opiate alkaloids. (C) 1997 Elsevier Science B.V.