Pharmacology: Intro to ANS 11/13 Flashcards
What is an agonist vs. an antagonist?
Agonists (activate)
- activate the receptor to signal as a direct result of binding to it
Antagonists (block activation)
- bind to receptors but do not activate generation of a signal
- interfere with the ability of an agonist to activate the receptor
Parasympathetic vs. Sympathetic
Parasympathetic: Craniosacral: “rest and digest”
- NT: ACh
- Receptors: nAChR, mAChR
Sympathetic:
- NT: NE>Epi (DA) ; ACh
- Receptors: alpha, beta (D), nACHR, mAChR
Acetylcholine (cholinergic)
- The major neurotransmitter of the parasympathetic nervous system
- All preganglionic autonomic fibers
- All postganglionic parasympathetic fibers
- Few postganglionic sympathetic fibers (sweat glands)
Norepinephrine (adrenergic)
- The major neurotransmitter of the sympathetic nervous system
- The vast majority of postganglionic sympathetic fibers
Epinephrine (adrenergic)
Synthesis only occurs in the adrenal medulla and in a few epinephrine-containing neuronal pathways in the brainstem
Dopamine
- NE and Epi precursor
- acts on the CNS and renal vascular smooth muscle
- synthesized in the cytoplasm of neurons
What occurs with junctional transmission?
AcCoA + Choline (in cytoplasm) via ChAT –> ACh
AcH transported into vesicle and is released into membrane when vesicle fusion occurs
where are nACHR (ionotropic) receptors located
Tissue Location:
- CNS Autonomic ganglia (PS) –> excitatory response
- Adrenal medula (S) –> release of catecholamines
Agonists:
- ACh
- Nicotine
mAChR (metabotropic)
Tissue location:
- CNS Autonomic Ganglia (PS)
- Effector Organs (cardiac, smooth muscle, gland cells, nerve terminals) (PS)
- Sweat glands (S)
–> In PS tissues results in excitatory and inhibitory effects, in sweat glands it results in sweat secretion
Agonists:
- ACh
- Muscarine
There are five subtypes of muscarinic receptors - the major ones being M2 and M3.
- M2;: present in heart, nerves, and smooth muscle - results in activation of PS system and slows down HR and decreases cardiac contraction
- M3: found in glands, smooth muscle, and and endothelium - results in constriction of smooth muscle of the lungs, and contraction of muscles.
What occurs at the adrenergic nerve terminal?
- synthesis : Tyrosine enters the terminal via Na+ dependent tyrosine transporter and is converted to Dopa via tyrosine hydroxylase. Dopa is converted to Dopamine in the cytoplasm.
- Storage: Dopamine enters the vesicle via the Vesicular Monoamine Transporter (VMAT-2) where it is converted into NE. NE is converted to Epi.
- Tyrosine –> Dopa –> Dopamine –> NE
- VMAT can be blocked by Reserpine
- release: NE is released (where it can go to stimulate receptors). It is taken back up by NE transporter (NET) -
* NET be blocked by cocaine, thus why cocaine is a stimulant.
Where does Catecholamine synthesis occur?
tyrosine –> dopa –> dopamine (occurs in the nerve cytoplasm)
dopamine –> NE (occurs only in vesicle)
NE–> epi (occurs mainly in the adrenal medulla)
What does VMAT do?
- Transports NE, Epi, DA, and serotonin into vesicles (promiscuous – shuttles in all NT’s into the vessicle)
- Release upon action potential and Ca2+ influx
- Can be blocked by Reserpine: Reserpine used to be used to decrease high blood pressure - no longer used b/c it reduces sympathetic tone in all organs.
How is catecholamine signaling terminated?
- Reuptake into nerve terminals: * major mechanism *
- NE transporter (NET) and Dopamine transporter (DAT)
- after reuptake, catecholamines are stored in vesicles by VMAT-2
- Metabolism of catecholamines
- Monoamine oxidase (MAO)
- Catechol-O-methyltransferase (COMT)
*In contrast to cholinergic signaling, termination of catecholamine action by degradative enzymes (i.e., AChE) is nonexistent in adrenergic signaling
Muscarinic Receptors
Contract smooth muscle (different intracellular signal than α1 receptors)
Apparent discrepancy – ACh & muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
- Blood vessels relax in response to parasympathetic release of ACh as long as the epithelium is intact: smooth muscle of blood vessels is NOT innervated by PS neurons
How do blood vessels relax?
- no PS neuronal stimulation
- Activation of mAChRs on epithelial cells causes production and release of endothelium-derived relaxing factor (EDRF), also known as nitric oxide (NO)
- Stimulation of NO release can occur from ACh, vasoactive
products, and physical stimuli - thus when people are constricted in their vessels, they are pumped up with NO rather than ACh (which would activate all smooth muscle) - so that only the blood vessels are affected.
