Lecture 12 Eicosanoids & Cannabinoids Flashcards
What do Eicosanoids do?
Play an important role in inflammation
Eicosanoids are generated from what?
Arachidonic Acid (Fatty Acid Precursor)
Prostaglandins
Eicosanoid
Prostanoid
Thromboxanes
Eicosanoid
Prostanoid
Leukotriene
Eicosanoid
Epoxyeicosatrienoic Acid (EET)
Eicosanoid
Arachidonic Acid Metabolism (How id AA made?)
Phospholipids –> Arachidonic Acid
Converted by Phospholipase A2
Arachidonic Acid Metabolism (What does AA make?)
Lipoxygenases (5-lipoxygenase) converts AA –> HPETE
HPETE can be made into Leukotrienes
COX1/COX2 converts AA into Prostanoids
Arachidonic Acid Metabolism (Prostanoids)
Depending on the environemnt and what enzymes are around Prostanoids are then converted into prostaglandins
Their are many types of Prostaglandins
Prostacyclin (Metabolism Path)
Prostanoid –> Prostacyclin (PGI2)
Initiated by Prostacyclin Synthase in Endothelium
Prostacyclin (Effects)
Inhibits Platelet Aggregation
Vasodilator
Thromboxane (Metabolism Path)
Prostanoid –> Thromboxane (TXA2)
Initiated by Thromboxane Synthase in Platelets
Thromboxane (Effects)
Promotes Platelet Aggregation
Vasoconstriction
PGD2
Prostanoid
Vasodilation
Inhibits Platelet Aggregation
Relaxes GI and Uterus Muscles
PGE2
Main Inflammatory Prostanoid
Vasodilator
Decrease Blood Flow by heat (Pyrogenic)
PGF(2-alpha)
Uterine Contractions
Alprostadil
PGE1
Vasodilation
Misoprostol
PGE2
Inhibits Gastric Acid secretion
Stimulates GI Muscous secretion
Uterine Contractions (Terminates Early Pregnancy)
Cervical Ripening/Dilation (Induce Labour)
Gemeprost
PGE2
Uterine Contractions (Terminates Early Pregnancy)
Dinoprostone
PGE2
Cervical Ripening/Dilation (Induce Labour)
Carboprost
PGF2-alpha
Uterine Contraction (Uses blood to cause)
Latanoprost
PGF2-alpha
Uterine Contraction
Also contracts eye to release fluid
Epoprostenol
PGI2
Inhibits Platelet Aggregation
Vasodilator (Treats Hypertension)
What are Leukotrienes made by?
White Blood Cells from arachidonic acid
What are the two receptor types for Leukotrienes
BLT
CysLT
LTB4
Binds to BLT receptors
Pro-inflammatory leukotriene
Stimulates neutrophil chemotaxis
Stimulates proliferation and cytokine production
By Macrophages and Lymphocytes
Cysteinyl Leukotrienes
Binds to CysLT Receptors
Contract Bronchi Muscles
Contracts cornea
Vasodilation in most other vessels
Zafirlukast
CysLT Receptor Antagonist
Treats Asthma (Prevents Bronchi Constriction)
Montelukast
CysLT Receptor Antagonist
Treats Asthma (Prevents Bronchi Constriction)
THC (Tetrahydrocannabinol)
Main psychoactive compound in Cannabis
CBD (Cannabinoid)
Non psychoactive compound in Cannabis, has some medicinal effects
Subjective Effects of THC
Relaxation
Sharpened Sensory
Mimics Psychosis
Objective Effects of THC
Increased Hunger
Impaired Motor Skills
Impaired Short-Term Memory
Antiemetic
Analgesia
Catalepsy
Peripheral Effects of THC
Vasodilation (More in the eyes)
Bronchodilation
Decreased Intraocular Pressure
Cannabinoid Receptor Types
What kind of receptors are they?
CB1 and CB2
Both are G-Protein (Gi or G0)
Inhibits AC
Inhibit voltage gated Ca2+ Channels
Hyperpolarization
CB1 (Where)
Brain
Pre-Synaptic and inhibit transmitter release
Endothelial cells, adipocytes, peripheral nerves
CB2 (Where)
Immune Cells
When is COX-1 active
Constitutive (Active all the time)
When is COX-2 active
Inducible (Activated by certain conditions)
Endocannabinoids
Natural cannabinoids made in the body from phospholipids
Retrograde Mediators (Signals from Postsynaptic –> Presynaptic)
Anandamide
Endocannabinoid
2-arachidonyl glycerol
Endocannabinoid
Endocannabinoids (Neuromodulatory Actions)
Nociception
Cardiovascular, GI, Respiratory Function
Food Intake/Appetite
Reproductive Function
Nabiximols
CB Agonist
Mix of THC & CBD
Treats Pain
Nabilone
Synthetic Cannabinoid
Treats Nausea and Vomitting associated with Chemotherapy
