Neuropharm GPCR Flashcards
G protein coupled receptors
Alpha 1 receptor
Alpha 2 receptor
Beta 1 receptor
Beta 2 receptor
The alpha 1 Adrenergic receptor is a G protein coupled receptor associated with the _ subunit
Gq
The Gq subunit associated with the alpha 1 receptor activates _____
Phospholipase c
What does phospholipase C do
Hydrolyzes PIP2 to DAG and IP2 in a signal transduction pathway
DAG
Second messenger that activates PKC
IP3
Plays role in phosphorylation of certain proteins
Catecholamines including ___ and ____ signal through the alpha 1 receptor in the central and peripheral nervous systems
Norepinephrine
Epinephrine
Effects of activation of alpha 1 receptor
Increased vascular smooth muscle contraction
Pupillary dilator muscle contraction
Intestinal and bladder sphincter muscle contraction
How remember a1
Alpha 1 receptor
Gq magazine model flexing arm holding a smoothie muscle
His purple purples are dilated and intestines and bladder flexing
How does alpha 1 effect pupillary dilator muscles
Contracts them
Also called myadrisis
The alpha 2 receptor is a GPCR associated with the _ subunit
Gi
The Gi subunit associated with the alpha 2 receptor does what
Inhibit production of Camp from ATP
Catecholamines like ___ and ___ signal through the alpha 2 receptor
Norepinephrine epinephrine
Where are alpha 2 receptors
On vascular prejunctional terminals
What does an activated alpha 2 receptor do
Inhibits the release of norepinephrine in a form of negative feedback
Effects of a2
Suppression of sympathetic outflow
Inhibition of insulin release from the pancreas
Inhibition of lipolysis in adipose tissue
Increased platelet aggregation
The beta 1 Adrenergic receptor is a GPCR associated with the ___ subunit
Gs
What does G2 subunit, associated with beta 1, do
Activates adenylate cyclase to activate the cAMP-dependent pathway
Effects of B1 activation
Increased cardiac output via an increase in heart rate
Increased cardiac contractility
Increased renin release from juxtaglomerular cells in the kidney
Increased lipolysis in adipose tissue
Name some selective b1 receptor agonist
Dobutamine
What use dobutamine for
Cardiogenic shock
Name some beta blockers
Atenolol
Esmolol
Metoprolol
The beta 2 Adrenergic receptor is a GPCR associated with the _ subunit
Gs
What does Gs associated with b2 do
Activates adenylate cyclase, which catalyze the formation of cAMP which activates protein kinase A.
Result of B2 activation
Increased heart rate and contractility
Increased lipolysis
Increased insulin release
Increased aqueous humor production and ciliary muscle relaxation causing increased intraocular pressure
Smooth muscle relaxation in uterus
Smooth muscle relaxation in bronchi causing bronchodilator
Vasodilation int he muscle and liver to air int he fight or flight response
Beta 2 agonists are contraindicated in ___
Glaucoma
Action of b2 on uterus clinically
Used to reduce uterine irritability and prevent or stop preterm labor
A1 receptors mediate ___, b2 receptors mediate ___ in the msucle and liver to air in fight or flight response
Vasoconstriction
Vasodilation
Release of insulin is strongly inhibited by ___, why
Norepinephrine
Leads to increased blood glucose levels during stress
But norepinephrine also activates b2 which stimulates insulin release. Why does norepinephrine inhibit insulin release
Dominance of the role of the alpha 2 receptor, which decreases insulin release from pancreas
When does lipolysis occur
When certain hormones that induce lipolysis trigger receptors that activate adenylate cyclase to increase production of cAMP, which activates lipases found in adipose tissue
How does a2 activation decrease lipolysis
Inhibits production of cAMP, activation of these receptors plays a role in decreasing lipolysis from adipose tissue as a part of negative feedback of the sympathetic pathway.
Platelates are also called
Thrombocytes
How does a2 increase platelet activation
Platelets aggregate together using fibrinogen and Von williebrand factor, and are stimulated by ADP, thromboxane and a2 activation
Inotropic effect
Actions of b1 receptor include increased atrial and ventricular contractility
What does inotropic effect lead to
Increased cardiac output in the sympathetic response
Effect of b1 on kidney
Increases renin release from juxtaglomerular cells in the kidney
What does renin do
Enzyme that breaks down angiotensinogen to angiotensin 1, which is further cleaved by ACE enzyme into angiotensin II
What does angiotensin II do
Constrict blood vessels, increases ADH secretion and aldosterone and stimulates the thirst reflex in the hypothalamus, leading to an increase in blood pressure
Effect of increased renin on bp
Increased bp in sympathetic response
How does b1 effect lipolysis
Activation leads to to increased lipolysis to help mobilize energy stores during the sympathetic response
What is lipolysis
Breakdown of lipids, which involves the hydrolysis of triglycerides into free fatty acids, which can undergo degradation by beta oxidation to produce energy for the body
B2 activation activates what
Adenylate cyclase, which catalyze the formation of cAMP, which activates PKA
How does b2 increase heart rate
SA node
Chronotropic effect
Chronotropic effect
Increased SA node rate
Increases cardiac output int he sympathetic response, although the effect is minor when compared to the beta1 receptor
Actions of b2
Increased atrial and ventricular contractility, known as inotropic effect
Inotropic effect
B2 increases atrial and ventricular contractility
What does inotropic effect of b2 lead to
Increased CO in the sympathetic response although the effects in minor when compared to the b1 receptor
Activation b2 lipolysis
Increases lipolysis to help mobiliza energy stores during the sympathetic response
B2 insulin
Decrease in secretion in sympathetic response
B2 eye
Increase aqueous humor in the eye
How treat glaucoma
B2 antagonists such as timolol
What are the ciliary muscles
Ring of smooth muscle in eye that controls accomodation for viewing objects and regulates the flow of aqueous humor into schlemms canal
B2 and ciliar muscle
Relaxation in sympathetic
Increase in ciliary body size
Effect of b2 relaxation of ciliary muscle on zonule fibers
Increases tension in zonule fibers of the eye, causing the lens to stretch flat, appropriate for far distance vision
Impedes aqueous flow leading to an increase in intraocular pressure
A1 receptors mediate ___, beta 2 receptors mediate ___ in the muscle and liver to aid in fight or flight
Vasoconstriction
Vasodilation
How treat asthma with b2 agonist
Bronchodilation
How can b2 agonist prevent or stop preterm labor
Smooth muscle relaxation int he uterus which reduce uterine irritability
Example of a b2 agonist used to decrease uterine tone as a tocolytic
Ritodrine
Non selective beta blockers
First generation b blockers have antagonistic effects at b1 and b2 preventing direct sympathomimetics such as norepinephrine and epinephrine from binding to these receptors
Where are b1 receptors
Heart kidney
Where are b2
Lung, peripheral blood vessels and skeletal muscle
What suffix do beta blockers have
Olol
How do non selective beta blockers work
Prevent the release of cAMP, a secondary messenger int he Gs protein signal transduction pathway. Without camp, protein kinase A remains inactivated and thus ca currents are reduced
Name the non selective beta blockers
Propranolol
Pindolol
Nadolol
Timolol
Proparnolol was first developed for what
Angina pactoris and then used as anti hypertensive
Not commonly used for these anymore
Why is propranolol not usually used usually for angina pectorals or as an antihypertensivee anymore
Side effects such as bronchospasm and thus exacerbation of chronic obstructive lung disease (COPD) and asthma
Depression
Exacerbation of peripheral arterial disease, and masking signs and symptoms of hypoglycemia in diabetics
What is propranolol used for now
Long term post MI
Atrial fibrillation, A-flutter
Treat thyroid storm - arrhythmias
Thryotoxicosis
Essential tremor
Prevention of bleeding esophageal varices
Akathisia and chronic migraine prophylaxis
Traditional use of nonselective beta blocker, timolol
First line therapy for the reduction of intraocular pressure in open angle glaucoma and is part of the empiric therapy for acute angle closure glaucoma
Timolol was initially shown to not be an effective systemic hypotensive agent, but when formulated into a ___ drug it was demonstrated to be extremely effective in reduction of IOP
Topical
But what is the preserved treatment for open angle glaucoma
Topical prostaglandins
Side effects timolol
Cardiac arrhythmia and severe bronchospasm
What is nadolol used for
Prevention of bleeding esophageal varices
Migraine headaches
Adult ADHD
Essential tremor and Parkinson’s disease
Side effects of nadolol
Bradycardia, fatigue and bronchospasms
Partial b agonists
Block b receptors but also have intrinsic sympathomimetic activity (ISA) and partially activate the receptor. At high doses they exert effects like epinephrine (increased pulse rate, increased blood pressure, bronchodilation)
Example of partial b agonist
Pindolol, Acebutolol, Labetalol
What is pinodolol used for
Treatment of angina pectoris and hypertension
Why is treatment with pindolol rarely used
Due to its intrinsic sympathomimetic activity (ISA)
Nonselective beta with alpha blocking
These drugs nonselectively block both b and a receptors . Their a blocking effects give them a vasodilatory effect Which potentiates the b blocking effect to reduce blood pressure
Examples of nonselective b with a blocking
Carvedilol
Labetalol
Carvedilol to treat what
CHF as an adjunct to conventional treatments (ACE inhibitors and diuretics)
Treat pregnancy induced hypertension and can be used 2nd line in hypertensive emergencies
Labetolol
Treatment of pregnancy induced hypertension and can be used 2nd line in hypertensive emergencies
Selective b blockers
Metoprolol, Betaxolol, Acebutolol, Atenolol
