Morphine and anandamide stimulate intracellular calcium transients in human arterial endothelial cells: coupling to nitric oxide release.
Both morphine and anandamide significantly stimulated cultured endothelial intracellular calcium level increases in a concentration-dependent manner in cells pre-loaded with fura 2/AM. Morphine is more potent than anandamide (approximately 275 vs. 135 nM [Ca]i), and the [Ca]i for both ligands was blocked by prior exposure of the cells to their respective receptor antagonist, i.e., naloxone and SR 171416A. Various opioid peptides did not exhibit this ability, indicating a morphine-mu3-mediated process. In comparing the sequence of events concerning morphine's and anandamide's action in stimulating both [Ca]i and nitric oxide production in endothelial cells, we found that the first event precedes the second by 40+/-8 sec. The opiate and cannabinoid stimulation of [Ca]i was attenuated in cells leeched of calcium, strongly suggesting that intracellular calcium levels regulate cNOS activity.
Fimiani
C
C
Multidisciplinary Center for the Study of Aging, Neuroscience Research Institute, State University of New York at Old Westbury, 11568-0210, USA.
Mattocks
D
D
Cavani
F
F
Salzet
M
M
Deutsch
D G
DG
Pryor
S
S
Bilfinger
T V
TV
Stefano
G B
GB
D000701:Analgesics, Opioid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D015398:Signal Transduction
D000701:Analgesics, Opioid; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D009569:Nitric Oxide; D009020:Morphine; D002118:Calcium; C078814:anandamide