Lecture_15_-_Atypical_Neurotransmitters

Cb receptors are located primarily on presynaptic

Info iconThis preview shows pages 16–24. Sign up to view the full content.

View Full Document Right Arrow Icon
CB receptors are located primarily on presynaptic terminals of both excitatory and inhibitory neurons where they inhibit neurotransmitter release Endocannabinoids are highly lipophilic and are derived from lipids in the plasma membrane. 2 major endogenous endocannabinoids: 2-arachidonylglycerol (2-AG) and anandamide (released in response to neuronal activity and activate CB1 receptors
Background image of page 16

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Endogenous endocannabinoids Both 2-AG and anandamide are synthesized from lipid precursors derived from the plasma membrane and release is coupled to synthesis (influx of Ca2+ actives synthetic enzymes) Synthesis can also be stimulated by activation of G-protein coupled receptors, specifically mGluRs and muscarinic receptors (i.e., Gq-coupled receptors which stimulate DAG production)
Background image of page 17
Both 2-AG and anandamide function as retrograde messengers (are released from postsynaptic membrane and bind to CB1 receptors located presynaptically) inhibit presynpatic activity (actions can last from seconds to hours)
Background image of page 18

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
CB1 activation also inhibits cAMP production. More longterm (and complicated) effects on gene expression and synaptic plasticity
Background image of page 19
Endocannabinoid signaling is terminated by their transport into cells and hydrolysis ( fatty acid amide hydrolase or FAAH breaks down anandamide and monoacylglycerol lipase or MGL breaks down 2-AG) Endocannabinoids can diffuse passively through membranes, but transport is facilitated by endocannabinoid transporters . This is an energy independent transporter, it just facilitates passive diffusion.
Background image of page 20

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Background image of page 21
The role of endocannabinoid signaling in the hippocampus Action potentials in hippocampal pyramidal neurons cause synthesis of 2-AG 2-AG diffuses out and activates CB1 receptors on GABA inter-neurons Reduction in GABA signaling, less inhibition of the pyramidal neuron May play a role in long term potentiation, but what happens when you flood your CB1 receptors with THC?
Background image of page 22

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Endocannabinoid system as a target for therapeutics CB1 receptor -stimulation induces feeding (“munchies”) antagonist (e.g., rimonbant ) used in Europe for the treatment of obesity -stimulation reduces nausea agonists (e.g., dronabinol ) used to treat sickness due to chemotherapy and for stimulating appetite in people with advances HIV/AIDS -stimulation is analgesic agonists reduce pain in neuropathic and inflammatory pain Degradative Enzymes (FAAH and MGL) -inhibition promotes actions of endocannabinoids on CB1 receptors pro-appetite, analgesic and anti-depressant properties (and appear to improve motor activity when combined with dopamine receptor agonists in models of Parkinson’s Disease) -have the advantage that enzyme antagonists would exert effects only at active synapses
Background image of page 23
Background image of page 24
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

Page16 / 24

CB receptors are located primarily on presynaptic terminals...

This preview shows document pages 16 - 24. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online