Cannabinoid Receptors Flashcards
Outline the steps taken and understanding the endocannabinoid system
Cannabinoid receptor discovery
Synthesis of specific agonists and antagonists
Discovery of the Endo cannabinoid system
True or false: cannabinoids are highly hydrophilic
False, they are highly lipophilic
How were cannabinoids first thought to exert their effects?
By disrupting the cell membrane in a non-specific manner
What were the two major findings related to the mechanism of cannabinoid action?
Cannabinoids act via G proteins
And the discovery of high affinity binding sites for cannabinoid molecules
When was Delta nine THC identified as the primary psychoactive component of cannabis?
1964
When was the CB1 receptor identified?
1988
When was the CB1 receptor cloned from a rat?
1990
When was the CB1 receptor cloned from a human?
1991
When was the CB2 receptor identified?
1993
Where are CB1 receptors located throughout the body? (Six)))
Brain
Liver
Reproductive system
Cardiovascular system
Skeletal muscle muscles
G.I. tract
Give examples of CB1 receptor function in the brain
Learning, memory, cognition
Motor control
Anxiety and depression
Appetite and food intake
Reward and addiction
Neuro protection
Neural development
Sleep
Give examples of CB1 receptor function in the liver
Ascites formation
Lipogenesis
Fibrosis
Insulin resistance
Give examples of CB1 receptor function in the reproductive system
Fertility regulation, embryo implantation
Embryonic development
Give example examples of CB1 receptor function in the cardiovascular system
Negative inotropy
Vasodilation
Cardiac function
Give example examples of CB1 receptor function in skeletal muscle
Energy metabolism
Muscle fibre formation
Give examples of CB1 receptor function in the G.I. tract
G.I. motility
Enteroendocrine function
Intestinal barrier function
Energy balance
Give examples of other CB1 receptor functions
Nociception
Immune modulation
Nausea and emesis
Intraocular pressure
Bone remodelling
Bronchodilation
Cancer
Is there a high or low concentration of cannabinoid receptors in the brain stem?
Low
What is a possible explanation as to why cannabis use is not associated with sudden death due to respiratory depression?
Due to the low concentration of receptors in the brain stem
What cannabinoid receptor is found predominantly in the central nervous system?
CB1
Where do CB2 receptors occur?
Immune system and other tissues, such as bone, adipose cells, and the G.I. tract.
What are some of the most abundant G protein linked receptors in the brain?
CB1 receptors
What does the localization of CB1 receptors mode of action suggest?
Primary function of these receptors might be to inhibit neurotransmitter release
What three things does CB1 receptor activation lead to and what is the overall effect of this?
Inhibition of cAMP
Inhibition of voltaGE sensitive calcium channels
Activation of potassium channel opening
These signalling events combined to exert a powerful inhibitory effect on neurotransmitter release
What neurotransmitters does the C1 receptor inhibit? (6)
Acetylcholine
Dopamine
Norepinephrine
Serotonin
GABA
Glutamate
What did the identification of CB receptors initiate?
Research for endogenous cannabinoid ligands
When was the first endocannabinoid identified and what was it?
1992
N-arachidonylethanolamine (anandamide)
When was the second endocannabinoid identified and what was it?
1995
2-arachidonoylglycerol (2-AG)
What is the Sanskrit meaning for Anandamine?
Internal bliss
How do 2-AG and anandamide act at CB1 and CB2 receptors
2-AG is a full agonist and anandamide is a partial agonist
What is the probable mechanism for removing endocannabinoids from the extracellular fluid?
Probably removed by a membrane transporter
How is anandamide metabolized?
By fatty acid amine Hydrolase [FAAH))
How is 2-AG metabolized?
By monoacyl-glycerol Lipase[MAGL)
How does the Endo cannabinoid system differ from other bodily systems in terms of our knowledge?
It is the most complicated and most abundant signalling system in our bodies that most people know nothing about
True or false the cannabinoid system performs the same tasks in each tissue
False, the system performs different tasks in each tissue
What is the goal of the endocannabinoid system?
To maintain homeostasis despite fluctuations in the external environment
What is homeostasis?
The ability to maintain stable internal conditions that are necessary for survival
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Give two examples of roles of the endocannabinoid system in the brain.
Synaptogenesis
Synaptic pruning
Give examples of some triggers the endocannabinoid system responds to. (5)
Singing
Dancing
Exercise
Stress
Time of day
Give examples of responses produced by the endocannabinoid system in (3)
Appetite
Coping with stress and anxiety
Pain relief
Give 2 examples as to why the endocannabinoid system is called “clever”
Learns from stress
AIDS in formation of helpful memories while preventing formation of harmful memories
Compare endocannabinoids with THC. (4)
ECs work right place right time, THC has multiple effects at once
ECs are precise, THC not
ECs are responsive, THC is not
ECs are tightly controlled, THC down regulates the EC system
What are the three key components of the EC system?
Cannabinoid receptors
Endocannabinoids
Metabolic enzymes
Give examples of pathways regulated by the EC system (9)
Gastrointestinal activity
Cardiovascular activity
Pain perception
Maintenance of bone mass
Protection of neurons
Hormonal regulation, metabolism control
Immune function
Inflammatory reaction
Inhibition of tumours
What is a main feature that distinguishes them from other neuromodulators/neurotransmitters?
They are not synthesized in advance and stored in vesicles
Describe the “on-demand” synthesis of ECs.
ECs have precursors that are cleaved by specific enzymes
What is Rimonabant?
CB1 receptor antagonist
An anti-obesity drug approved Igor use in Europe in 2006
Suppresses appetite and reduces cravings for sweet foods
But induces symptoms of anxiety and depression
Eupho
Give examples of subjective effects of cannabinoids (4)
Euphoria
Exhilaration
Disinhibition
Relaxation
Give examples of sensory reactions to cannabinoids (4)
Floating sensations
Enhanced visual and auditory perception
Visual illusions
Slowing of time passage
Give examples of physiological effects of cannabinoids (3)
Increased blood flow to skin and flushing
Increased heart rate
Increased hunger
What are cannabis effects mediated by (at least partially) and what happens to effects after pretreatment with rimonabrant?
CB1 receptor
Effects significantly reduced
What happens in terms of pain regulation in CB1 and CB2 knockout mice or mice treated with rimonabrant?
Have hyperalgesia (greater pain sensitivity)
How do CB1 and CB2 receptors contribute to pain regulation?
Regulate both pain perception and cognitive-affective responses to pain
Why might the EC system be a prime target for new therapeutic approaches to neuropathic pain, as opppsed to opioids?
Neuropathic pain is produced within the nervous system itself, not in direct response to a nociceptive stimulus
Opioid drugs are ineffective for this type of pain
Describe the EC system as it relates to aggression.
Low dose THC shown to reduce the frequency of attacks by resident animals in a dose-dependent manner
Describe animal studies regarding violence and cannabinoids
Low dose THC shown to reduce the frequency of attacks by resident animals in a dose-de
