Neuroscience 2000 Abstract
| Presentation Number: | 813.7 |
|---|---|
| Abstract Title: | Role of fatty acid amidohydrolase in the uptake of the endogenous cannabinoid anandamide. |
| Authors: |
Day, T. A.*1
; Rakhshan, F.1
; Barker, E. L.1
1Dept Medicinal Chem Molec Pharmacol, Purdue Univ, West Lafayette, IN |
| Primary Theme and Topics |
D. Neurotransmitters, Modulators, Transporters, and Receptors - 54. Cannabinoids |
| Secondary Theme and Topics | D. Neurotransmitters, Modulators, Transporters, and Receptors<br />- 58. Uptake and transporters |
| Session: |
813. Cannabinoids: anandamide Poster |
| Presentation Time: | Thursday, November 9, 2000 10:00 AM-11:00 AM |
| Location: | Hall G-J |
| Keywords: | TRANSPORT**, THC, INHIBITION**, METABOLISM** |
The endogenous cannabinoid anandamide (N-arachidonylethanolamide) is a long chain fatty acid amide that is capable of activating the cannabinoid receptors similar to Δ9-tetrahydrocannabinol, the active ingredient in marijuana. Anandamide is a putative neurotransmitter with inactivation occurring through a facilitative uptake process with subsequent intracellular metabolism by fatty acid amidohydrolase (FAAH). We propose that FAAH may participate in the anandamide uptake process by creating and maintaining an inward concentration gradient of anandamide. To determine the role of FAAH in anandamide uptake, we have heterologously expressed FAAH cDNA in wild-type HeLa cells. Results demonstrated a lack of FAAH in HeLa cells as determined by RT-PCR of total HeLa RNA and a FAAH enzymatic assay. Interestingly, both wild-type and FAAH-transfected HeLa cells showed similar anandamide transport activity. However, FAAH-transfected HeLa cells had a 3-fold increased ability to metabolize anandamide. Furthermore, the addition of the FAAH inhibitor methyl arachidonyl fluorophosphonate (MAFP) reduced this enzymatic activity to that of wild-type HeLa cells. Likewise, anandamide transport was significantly reduced in both the native and transfected cells by MAFP and the anandamide transport inhibitor AM404. Our results suggest that MAFP, in addition to inhibiting FAAH, may be capable of directly inhibiting the protein(s) responsible for anandamide uptake. Additional investigation into the component(s) directing anandamide transport in HeLa cells may further elucidate FAAH's involvement in anandamide uptake.
Supported by Purdue Univ.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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