Pharmacology of N-acylethanolamines and related vanilloid receptor modulators
Principal investigator; Högestätt, Edward, Professor, MD/PhD
Clinical speciality: Clinical pharmacology
Phone: +4646-173358
Co-workers: Associate professor Peter Zygmunt, Associate professor Lennart Greiff, Professor Bo Jönsson, Professor Olov Sterner
This project is based on our original discovery that anandamide, an endogenous long chain N-acylethanolamine, activates vanilloid receptors (TRPV1) on nociceptive primary sensory nerves. Anandamide belongs to a novel group of bioactive lipids, having interesting effects on neuronal signaling in the pain pathway.
The aims of this project are (key techniques within brackets): 1. To identify additional endogenous TRPV1 ligands (mass spectrometry, various bioassays). 2. To measure the levels of anandamide and related lipids in inflammation and tissue injury (mass spectrometry). 3. To investigate why some TRPV1 agonists are pungent while others are lacking this unwanted side effect (patch-clamp, calcium imaging, in vivo models of pain). 4. To develop methods for studying the effects of TRPV1 modulators in man (measurement of skin blood flow).
The molecular mechanisms of pain are poorly understood. This project, which focuses on the role of anandamide and related endogenous lipids in the pain pathway, may provide novel targets and lead compounds for drug development. Drugs acting on TRPV1 may be used not only as analgesics, but also for treatment of diseases involving dysfunction of primary sensory nerves, such as bladder overactivity. Methods to predict pungency of TRPV1 agonists would be extremely valuable in screening assays for novel analgesics.
Link to project homepage: http://www.med.lu.se
5 recent original publications
Movahed P, Evilevitch V, Andersson TLG, Jönsson BAG, Wollmer P, Zygmunt PM, Högestätt ED
Vascular effects of anandamide and N-acylvanillylamines in the human forearm and skin microcirculation
Br J Pharmacol. 2005; 145: in press
Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID and Julius D
Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1
Nature. 2004; 427: 260-265
Zygmunt PM, Andersson DA, Hogestatt ED
Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism
J Neurosci. 2002; 22: 4720-4727
Andersson DA, Adner M, Högestätt ED and Zygmunt PM
Mechanisms underlying tissue selectivity of anandamide and other vanilloid receptor agonists
Mol Pharmacol. 2002; 62: 705-713
Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D and Högestätt ED
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Nature. 1999; 400: 452-457
Further publications here (new window)
Financing/year
| Total financing: | 2,5 MSEK | Gov grant for clinical research ("ALF"): | MSEK | |
| Total external financing: | MSEK | Natl and intl prioritized grants: | MSEK |