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 us. 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-mu(3)-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. CELL SIGNAL 11;3:189-193, 1999. (C) 1999 Elsevier Science Inc.