Intro to Autonomic Pharm Flashcards
The ANS is not influenced by voluntary control and it regulates:
- contraction and relaxation of smooth muscle
- all exocrine and certain endocrine secretions
- heartbeat
- certain steps in intermediary metabolism
In the heart the CNS/PNS dominates
PNS (parasympathetic nervous system)
The control of blood pressure is mainly sympathetic/parasympathetic
Sympathetic
Sweat glands, kidney and the adrenal medulla are innervated only by _________
Sympathetic
What are the cholinergic fibers?
- ALL preganglionic autonomic fibers
- all parasympathetic post ganglionic fibers
- all somatic motor fibers to skeletal muscle
Example of a sympathetic chilinergic fiber?
Sweat glands; they are sympathetic fibers that release acetylcholine
The ______________ fibers in the kidney release ____________ that act on the renal vascular smooth muscle
Sympathetic; dopamine
What is the rate limiting step in the synthesis of acetylcholine?
Bringing in choline into the neuron via the CHT1 transporter that also requires sodium (symport)
M2 muscarinic receptor is found on __________________ and is ___________
Presynaptic neuron; inhibitory in action by binding and inactivating acetylcholine
Where is dopamine converted into NE?
Inside the vesicle
The α 2 adrenergic receptor on the _________ neuron causes ________
Presynaptic;
↓ further release of NE
What are the two types of cholinergic receptors?
- nicotinic (ion channel linked) : neuronal and muscle type
- muscarinic (G protein linked)
Neuronal nicotinic receptors are found on ________
Plasma membranes of the cell bodies of POST ganglionic parasympathetic and sympathetic receptors
Where can muscarinic receptors be found?
- organs innervated by parasympathetic nerves
- can be found in tissues that are NOT innervated by parasympathetic nerves BUT have these receptors but can get activate (endothelial cells)
- tissues innervated by cholinergic postganglionic nerves (sweat glands which are sympathetic)
Where can M1 receptors be found and what are the effects
- ganglia, CNS and vomiting center
- causes: depolarization, ↑ cognitive function, and emesis
Where can M2 receptors be found and what are the effects?
- heart (atria), presynaptic Nerve terminal s
- cardiac inhibition and inhibition of acetylcholine release
Where are M3 receptors located and what are the effects
- smooth muscles, secretory glands, vascular endothelium
- contraction of smooth muscle
- secretion
- vasodilation of vascular endothelium (only receptors are found here)
Endothelial cells that line blood vessels have uninnervated M3 receptors contain the enzyme __________ which catalyzes: _________
NO synthase; formation of NO from arginine
What is the effect of NO on the smooth muscle cells?
NO activates guanylyl sh last which causes the formation of cGMP from GTP
- cGMP activates a kinase which then phosphorylates proteins → relaxation of smooth muscle → vasodilation
All___________ receptors are G protein coupled receptors
Adrenergic
All β adrenergic receptors activate __________ via interaction with ______
Adenylyl cyclase; Gs
_______ and_______ of the β adrenergic receptors have equal affinity for _________ and ______
β1 and β3; NE and epinephrine
β2 has higher affinity for ________
epinephrine
Tissues with ________ receptors such as the vasculature of skeletal muscle are responsive to circulating ____________ released by the adrenal medulla
Β2; epinephrine
Where are α1 and β1 receptors found and what is the importance of their location
Found near the adrenergic nerve terminals so they can be activated when the nerves are stimulated
Where are α2 and β2 receptors located? What is the effect of their location on their activation?
- Located at sites remote form the nerve terminals
- they are activated preferentially by circulating epinephrine
Α2 and β2 receptors are activated preferentially by __________
Circulating epinephrine
What it the signaling method of β1 receptors?
↑ cAMP; Gs
What are the specific locations of the β1 receptor
- heart
- Juxtaglomerular (JG) cells
- adipocytes
What are the effects on the heart when the β1 receptors are activated?
↑ Heart rate
↑ Heart force
↑ AV conduction velocity
What is the effect on the JG cells when the _____ receptors are activated
β1;
↑ renin release
What is the effect of β1 receptor activation on adipocytes?
↑ lipolysis
What is the effect on the activation of ______ receptors on the pancreatic cells?
β2;
- pancreatic β cells: ↑ insulin secretion
- pancreatic α cells: ↑ glucagon secretion
Where can you find β2 receptors? (6)
- smooth muscle
- skeletal muscle
- pancreatic α cells
- pancreatic β cells
- liver
- adipocytes
What is the effect of activation of β2 receptors on skeletal muscle?
↑ glycogenolysis
↑ K+ uptake
What is the signaling mechanism of β receptors?
Gs coupled; ↑ cAMP etc
What is the signaling mechanism for α1 receptors and where are they located?
↑ IP3 and DAG ↑ Calcium; Gq
Located at: vascular and genitourinary SM and the liver
What is the effect of α1 receptors at the smooth muscles?
Vascular and genitourinary SM → contraction
What is the signaling mechanism for α2 receptors?
↓ cAMP through Gi → inhibition of NE release, inhibition of lipolysis
What is the effect of α2 receptors on platelets, pancreatic ____ cells and the vascular smooth muscle?
- platelet aggregation
- ↓ insulin secretion
- contraction
Where can the α2 receptors be found?
- presynaptic nerve terminals
- platelets
- adipocytes
- pancreatic β cells
- vascular SM
____ and _____ receptors act on the pancreatic β cells but _____ has more power and leads to a net effect of _____
α2 and β2 receptors;
α2 has more effect leading to an over effect of ↓ insulin secretion
What do you have more of in the vascular smooth muscle: α1 or α2 receptors?
α1
Dopamine receptors are predominately found in _______________ causing _________
Smooth muscle of renal vascular bed; relaxation and thus improving blood flow to the kidney
The receptor found in the salivary glands are ______
Parasympathetic cholinergic M3 receptors
The primary controlled variable in the cardiovascular function is the __________
Mean arterial pressure
What is the net effect of NE on the heart when accounting of the negative feed back baroeceptor response (homeostasis)?
- ↑ peripheral vascular resistance (contraction of SM)
- moderate ↑ in MAP
- BRADYCARDIA (opposite of drugs direct action)
The cells of the medulla are modified __________ ___________ neurons
Post ganglionic sympathetic
Describe the uniqueness of the innervation of sweat glands
They have sympathetic fibers that release acetylcholine and act on muscarinic receptors
(all other post ganglionic sympathetic fibers act on either α or β adrenoreceptors aka they are noradrenergic and act by releasing NE)
Dopamine is released by some peripheral _________ fibers
Sympathetic
What is the enzyme that synthesizes acetylcholine from acetyl CoA and choline?
Choline acetyltransferase (ChAT)
Synthesis of all catecholamines in the nervous systems originates from the amino acid ____________
Tyrosine
What is the rate limiting step in the creating of dopamine?
Tyrosine → L-DOPA which is done by the enzyme tyrosine hydroxylase
________ receptor actuation are response for the vagal inhibition fo the heart and the CNS and periphery
M2
________ activates endothelial nitric oxide synthase leading to the formation of NO from _________
Calcium;
Arginine
How does the release of NO lead to vasodilation?
NO binds to and activates guanylyl cyclase which catalyzes the formation of cGMP which ten acres the cGMP dependent protein kinase → phosphorylates proteins → vasodilation
NE stimulates renin secretion by directly acting on juxtaglomerular cells of the kidney as is mediated by _________ receptors
β1 adrenergic receptors
