Morphine and Anandamide Stimulate Intracellular Calcium Transients in Human Arterial Endothelial Cells: Coupling to Nitric Oxide Release

• Published in: Cellular signalling 1999-03, Vol.11 (3), p.189-193
• Main Authors: Fimiani, Caterina, Mattocks, Dwight, Cavani, Francesco, Salzet, Michel, Deutsch, Dale G., Pryor, Stephen, Bilfinger, Thomas V., Stefano, George B.
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Arachidonic Acids - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cells, Cultured; Dose-Response Relationship, Drug; Endocannabinoids; Endothelia, morphine, anadamide, calcium transients, nitric oxide, μ 3 receptor; Endothelium, Vascular - metabolism; Humans; Morphine - pharmacology; Nitric Oxide - metabolism; Polyunsaturated Alkamides; Signal Transduction
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/S0898-6568(98)00060-6

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-μ 3-mediated process. In comparing the sequence of events concerning morphine's and anandamide's action in stimulating both [Ca] i and nitric oxide (NO) 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 NOS activity.