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Delta9-tetrahydrocannabinol activates [Ca2+]i increases partly sensitive to capacitative store refilling
C M Filipeanu1, D de Zeeuw, S A Nelemans
1Groningen Institute of Drug Research, Department of Clinical Pharmacology, University of Groningen, The Netherlands.
European Journal of Pharmacology
|February 12, 1998
Summary
Delta9-tetrahydrocannabinol increases intracellular calcium in smooth muscle cells, primarily through calcium entry. This occurs via CB1 receptor stimulation and an additional pathway, independent of CB1 and CB2 receptors.
Area of Science:
- Cellular Biology
- Pharmacology
- Physiology
Background:
- Cannabinoids, including Delta9-tetrahydrocannabinol (THC), interact with specific receptors in the body.
- Smooth muscle cells play a critical role in various physiological processes.
- Understanding the mechanisms of THC's action on cellular calcium is crucial for pharmacology.
Purpose of the Study:
- To investigate the effects of Delta9-tetrahydrocannabinol on intracellular calcium ([Ca2+]i) levels in DDT1MF-2 smooth muscle cells.
- To elucidate the specific pathways involved in THC-induced calcium mobilization, including receptor-mediated and non-receptor-mediated mechanisms.
Main Methods:
- Concentration-dependent stimulation of DDT1MF-2 cells with Delta9-tetrahydrocannabinol.
- Functional downregulation of intracellular calcium stores using thapsigargin.
- Selective inhibition of cannabinoid receptors using SR141716A (CB1 antagonist) and palmitoylethanolamide (CB2 agonist).
- Measurement of intracellular calcium ([Ca2+]i) changes.
Main Results:
- Delta9-tetrahydrocannabinol induced concentration-dependent increases in intracellular calcium ([Ca2+]i).
- Both calcium entry and release from intracellular stores were observed, with calcium entry being the predominant component.
- Even after depleting intracellular stores, THC still stimulated significant calcium entry and minor release.
- CB1 receptor antagonist SR141716A inhibited thapsigargin-sensitive calcium influx and release.
- CB2 receptor agonist palmitoylethanolamide had no effect on [Ca2+]i.
- An additional THC-induced, thapsigargin-insensitive calcium influx was identified, not mediated by CB1 or CB2 receptors.
Conclusions:
- This study demonstrates CB1 receptor-mediated calcium release from thapsigargin-sensitive stores and capacitative calcium entry.
- It also reveals a novel, non-CB1/non-CB2 mediated Delta9-tetrahydrocannabinol-induced calcium influx pathway.
- These findings provide new insights into the complex mechanisms of cannabinoid action on smooth muscle cells.