Anandamide amidase inhibition enhances anandamide-stimulated nitric oxide release in invertebrate neural tissues.
Anandamide, an endogenous cannabinoid signaling molecule, in a concentration dependent manner, initiates the release of nitric oxide (NO) from leech and mussel ganglia. SR 141716A, a cannabinoid antagonist, blocks the anandamide stimulated release of NO from these tissues. Methyl arachidonyl fluorophosphonate (MAFP), a specific anandamide amidase inhibitor, when administered to either ganglia with anandamide (10-6 M) did not increase the peak level of NO release but did significantly extend NO release from 12 to 18 min (P<0.05). Lower levels of anandamide (10-8 and 10-7 M) do not stimulate the release of significant amounts of NO from these tissues. However, in the presence of MAFP (2.5 nM), the lower anandamide concentrations were able to release significant peak amounts of NO. In mussel neural tissues, the peak NO release increased from 2.2+/-1.3 nM to 8.6+/-2.1 nM. Taken together, the results indirectly demonstrate the presence of anandamide amidase in these tissues, suggesting that the enzyme may serve as an endogenous regulator of anandamide action.
Stefano
G B
GB
Multidisciplinary Center for the study of Aging, Neuroscience Research Institute, State University of New York at Old Westbury, Old Westbury, NY 11568-0210, USA. gstefano@li.net
Rialas
C M
CM
Deutsch
D G
DG
Salzet
M
M
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D049872:Bivalvia; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D063388:Endocannabinoids; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007865:Leeches; D009569:Nitric Oxide / Q000378:metabolism*; D053284:Polyunsaturated Alkamides
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D009569:Nitric Oxide; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase; C078814:anandamide