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+
