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Title: Modulation of anandamide actions on the neonatal rat cultured sensory neurone
Author: Khairy, Hesham A.
ISNI:       0000 0004 2700 6525
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2010
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The possible role of L-serine as an allosteric modulator of anandamide (AEA) action on cannabinoid receptors has been investigated along with the studying the actions of AEA metabolite, ethanolamine.  Dorsal root ganglia (DRG) neurons from neonate Sprague Dawley rats were used in primary culture. L-serine was found to modulate anandamide actions on overall neuronal excitability, voltage-activated K+ and Ca2+ currents and intracellular Ca2+ flux.  These modulations were suggested to be mediated via allosteric modulation of AEA actions at CB1 receptors.  These observations strengthen previous data obtained from binding studies of L-serine at CB1 receptors.  Furthermore, these modulations were abolished by CB1 antagonist, SR141716A, while L-serine alone failed to activate CB1 receptors.  We found that L-serine modulations were AEA-dependent and CB1 mediated, while no modulatory effects for L-serine were reported on TRPV1 or GPR55 receptors.  Similar modulations were reported from the CB1 allosteric modulator, Org-27569. Ethanolamine was fond to enhance the intracellular Ca2+ level via influencing thapsigargicin- and caffeine-sensitive calcium stores.  Ethanolamine actions were not abolished in PTX-treated DRG neurones or in the presence of CB1 antagonist, SR141716A indicating that these actions were conducted independently from CB1 receptors and inhibitory G-proteins. Additionally, ethanolamine modulated the voltage- activated potassium currents independently from its effect on intracellular Ca2+ level. In conclusion CB1 receptor modulation by ligands acting at an allosteric site may provide a novel approach to endocannabinoids-mediated therapies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cannabinoids ; Neurotransmitters