Introduction to Pharmacology of the autonomic nervous system Flashcards
what are some examples of drug targets found in the body?
Proteins:
- Hormone Growth Factor
- Growth factors
- Transcription factor receptors
- Nerurotransmitter receptors
- Ion channerls
- Enzymes
- Transport proteins
- Enzymes
- Transport proteins
what are the main neurotransmitters, and receptors for the parasympathetic Nervous system
Neurotransmitter: ACh
Receptors: nAChR, mAChR
What are the main neurotransmitters and receptors for the sympatheric nervous system
Neurotransmitters: NE>Epi (DA); ACh
receptors: alpha, beta, (D), nAChR, mAChR
where is the Acetylcholine Neurotransmitter found in the ANS
- Major neurotransmitter of the PNS
- All preganglionic autonomic fibers
- All postganglionic parasympathetic fibers
- Few postganglionic sympathetic fibers (sweat glands)
where is the Norepinephrine (adrenergic) neurotransmitter found in the ANS
- Major neurotransmitter of the sympathetic nervous system
- Vast majority of postganglionic sympathetic fibers
where is the Epinephrine neurotransmitter found in the ANS
Synthesis only occurs in the adrenal medulla and in a few epinephrine containing neuronal pathways in the brain stem
where is Dopamine found in the ANS
NE and Epi precursor
-acts on the CNS and the renal vascular smooth muscle
Review of the cholinergic neurotransmitter
1) choline enters the cell and combines with AcCoA
- choline can get blocked by Hemicholinium
2) ACh is packaged into Vesicles for storage and transport
- can be blocked via Vesamicol
3) ACh is released into the synapse via VAMPS and SNAPS when the Action potential comes and an enter of Ca into the cell
- release of ACh can be blocked by Botulinium Toxin
4) Ach destruction via acetylcholinesterase
Receptor, Tissue Location, Function, and Agonists of the nAChR
ionotropic,
Tissue Location: CNS
- Autonomic ganglia (Nn)
- Adrenal medula for sympathetic NS
Function: Excitatory
-release of catecholamines for SNS
Agonists:
Acetylcholine, Nicotine
Receptor, Tissue Location, Function, and Agonists of the mAChR
metabotropic
Tissue Location: CNS
- Autonomic ganglia
- Effector organs (cardiac and smooth muscle, gland cells, nerve terminals)
- Sweat glands for the SNS
Function: Excitatory and inhbitory
Agonists: Acetylcholine
muscarinic
Cholinergic Receptors, Location, Structural Features, Mechanism: M1
Receptor Type: M1
Location: CNS, ganglia
Structural Features: GPCR, Gq/11
Mechanism: Activation of Phospholipase C; IP3; DAG cascade
Cholinergic Receptors, Location, Structural Features, Mechanism: M2
Receptor Type: M2
Location: Heart, nerves, Smooth muscle
Structural Features: GPCR, Gi/o
Mechanism: Inhibition of adenyl cyclase decrease in cAMP production, activation of K+ channels
Cholinergic Receptors, Location, Structural Features, Mechanism: M3
Receptor Type: M3
Location: Glands, Smooth muscle, endothelium
Structural Features: GPCR, Gq/11
Mechanism: Activation of PLC; IP3; DAG cascade
Cholinergic Receptors, Location, Structural Features, Mechanism: M4
Receptor Type: M4
Location: CNS
Structural Features: GPCR, Gi/o
Mechanism: Inhibition of AC; decrease in cAMP and activation of K+ channels
Cholinergic Receptors, Location, Structural Features, Mechanism: M5
Receptor Type: M5
Location: CNS
Structural Features: GPCR, Gq/11
Mechanism: Activation of PLC; IP3; DAG cascade
Cholinergic Receptors, Location, Structural Features, Mechanism Nm
Receptor Type: Nm
Location: Skeletal muscle neuromuscular junction
Structural Features: Ligand gated ion channel
Mechanism: N+, K+ depolarizing ion channel
Cholinergic Receptors, Location, Structural Features, Mechanism Nn
Receptor Type: Nn
Location: Postganglionic cell body, dendrites, CNS
Structural Features: Ligand gated ion channel
Mechanism: N+, K+ Depolarizing ion channel
How does catecholamines synthesis occurs and in what locations?
Tyrosine to DOPA to Dopamine
-occurs in the nerve cytoplasm
Dopamine to Norepinephrine to eninephrine
-Occurs in the vesicle
Norepinephrine to epinephrine
-occurs mainly in the adrenal medulla
Synthesis, Storage, release, reuptake of Catecholamines
Na+ dependant tyrosine transporter
-transports tyrosine into the nerve terminal
Vesicular Monomine transporter (VMAT-2)
- Transports NE, Epi, DA and serotonin into the vesicles
- can be blocked via reserpine
- release upon action potential and Ca+ influx
NE tranporter (NET)
- IMports NE into the nerve terminal
- DAT imports DA into the nerve termina
Termination of the catecholamine signaling:
Reuptake into the nerve terminals
- Major mechanism that terminates catecholamines
- NET and DAT
- After reuptake, catecholamines are stored in vesivles by the VMAT-2
Metabolism of catecholamines (2 main enzymes)
- Monoamine oxidase (MAO)
- Catechol-O-methyltransferase (COMT)
degradative enzymes is nonexistent in adrenergic signaling
Receptor, G protein and effectors, Agonists, Tissue, Responses of: Alpha 1 adrenergic receptors
Receptor: Alpha 1
Gprotein: Gq, increase in phospholipase C; IP3; DAG to increase intracellular Ca
Agonist: Epi>NE
Tissue: Vascular, GU smooth muscle, liver, intestinal smooth muscle, heart
Responses: Contraction, GLycogenolysis, gluconeogenesis, hypepolarization and relaxation, increased contractile force; arrythmias
Receptor, G protein and effectors, Agonists, Tissue, Responses of: Alpha 2 adrenergic receptors
Receptor: Alpha 2
Gprotein: Gi, decrease in adenyl cyclase, decrease in cAMP
Agonist: Epi>NE
Tissue: Pancreatic islets, platelets, nerve terminals, vascular smooth muscle
Responses: Decreased insulin secretion, aggregation, decreased release of NE, contraction
Receptor, G protein and effectors, Agonists, Tissue, Responses of: Beta 1 adrenergic receptors
Receptor: Beta 1
Gprotein: Gs, increase adenyl cyclase, increase cAMP, increase of L type Ca channels
Agonist: Epi=NE
Tissue: Juxtaglomerular cells, Heart
Responses: increased renin secretion, increased force and rate of contraction of AV nodal and conduction velocity
Receptor, G protein and effectors, Agonists, Tissue, Responses of: Beta 2 adrenergic receptors
Receptor: Beta 2
Gprotein: Gs, increase adenyl cyclase, increase cAMP, increase of L type Ca channels
Agonist: Epi»NE
Tissue: Smooth muscle (vascular, bronchial, GI, GU)
Skeletal muscle
Responses: Relaxation
Glycogenolysis, uptake of K+
Receptor, G protein and effectors, Agonists, Tissue, Responses of: Beta 3 adrenergic receptors
Receptor: Beta 3
Gprotein: Gs, increase adenyl cyclase, increase cAMP, increase of L type Ca channels
Agonist: Epi>NE
Tissue: Adipose tissue
Responses: Lipolysis
what is the preference of Epinephrine and Norepinephrine to adrenergic receptors
Epinephrine (a1 = a2, B1 = B2)
Norepinephrine (a1 = a2, B1»_space;B2)
Rule of thumb for the Alpha 1 receptors
- Stimulate contraction of all smooth muscle
- Vascular smooth muscle: vasoconstriction
if inhibit theses than the opposite happens
Rule of thumb for the Beta 2 receptors
Relax smooth muscle = vasodilation
if inhibit these the opposite happens
Rule of thumb for the Muscarinic receptors
Contract smooth muscle (different intracellular signal than a1 receptors)
inhibit these the opposite will happen
How is that there is no Parasympathetic innervation to blood vessels but, parasympathetic activity causes vasodilation?
due to the parasympathetic innervation to the endothelium which releases NO causing vasodilation
Response of Blood vessels to autonomic nerve impulses
Sympathetic = constriction
parasympathetic: indirectly causues vasodilation by telling endothelium to release NO
How is the Adrenal Medulla innervated and what neurotransmitter/ receptor does it?
Sympathetic innervation
- Epi and NE release is triggered by the releaseof ACh from the preganglionic fibers
- Ach binds to NnAChRs and produce a localized depolarization
releases 80 percent Epi and 20 percent NE
Cholinomimetic Agents?
drugs that mimic ACh
- AChR agonists
- Acetylcholinesterase inhibitors
Colinoreceptor - blocking drugs
AChR antagonists
Sympathomimetic agents
Drugs that mimic or enhance alpha and B receptor stimulation
-Agonists that enhance catecholamine release, drugs that block reuptake
Adrenoreceptor-blocking drugs
alpha and beta antagonists
