Delta9-tetrahydrocannabinol activates [Ca2+]i increases partly sensitive to capacitative store refilling.
Delta9-tetrahydrocannabinol induces [Ca2+]i increases in DDT1MF-2 smooth muscle cells. Both Ca2+ entry and release from intracellular Ca2+ stores were concentration dependently activated. The Ca2+ entry component contributed most to the increases in [Ca2+]i. Stimulation with delta9-tetrahydrocannabinol after functional downregulation of intracellular Ca2+ stores by longterm thapsigargin treatment, still induced a major Ca2+ entry and a minor Ca2+ release component. Thapsigargin sensitive influx and release were selectively inhibited by the cannabinoid CB1 receptor antagonist SR141716A. No effects on [Ca2+]i were obtained after stimulation with the CB2 receptor agonist palmitoylethanolamide. This study is the first demonstration of (1) Ca2+ release from thapsigargin sensitive intracellular stores and capacitative Ca2+ entry via CB1 receptor stimulation and of (2) an additional delta9-tetrahydrocannabinol induced thapsigargin insensitive component, mainly representing Ca2+ influx which is neither mediated by CB1 nor CB2 receptor stimulation.
Filipeanu
C M
CM
Groningen Institute of Drug Research, Department of Clinical Pharmacology, University of Groningen, The Netherlands.
de Zeeuw
D
D
Nelemans
S A
SA
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D013759:Dronabinol / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000502:physiology; D019284:Thapsigargin
D004791:Enzyme Inhibitors; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D019284:Thapsigargin; D013759:Dronabinol; D002118:Calcium