Morphine and anandamide stimulate intracellular calcium transients in human arterial endothelial cells: coupling to nitric oxide release

Cell Signal. 1999 Mar;11(3):189-93. 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-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Arachidonic Acids / pharmacology*
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endocannabinoids
  • Endothelium, Vascular / metabolism*
  • Humans
  • Morphine / pharmacology*
  • Nitric Oxide / metabolism*
  • Polyunsaturated Alkamides
  • Signal Transduction


  • Analgesics, Opioid
  • Arachidonic Acids
  • Calcium Channel Blockers
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Nitric Oxide
  • Morphine
  • Calcium
  • anandamide