Overview of Neurotransmission Flashcards
what is an agonist that directly interacts with Nn receptors
nicotine
what is a partial agonist that directly interacts with Nn receptors
varenecline (chantix)
what is an antagonist that directly interacts with Nn receptors
mecamylamine
action of succinylcholine
a noncompetitive, depolarizing Nm blocker (cannot reach Emax)
action of CURare derivatives
nondepolarizing Nm blocker (competitive) (can still reach Emax)
example of CURare derivative
roCURonium (zemuron )
what are 5 targets for neurotransmitters?
- synthesis
- storage
- release
- termination of action
- receptor (direct)
4 indirect targets of NT
synthesis, storage, release, termination of action
direct target of NT
receptors
role of adrenal medulla in sympathetic activation
releases 80% epinephrine and 20% norepi in response to ACh stimulation
receptor type on sweat glands
Muscarinic receptors (M3) on erector pili and sweat glands, even though anatomically sympathetic (but postgang fibers release ACh)
what receptors are associated with the enteric nervous system
oral and aboral
what are oral receptors for
control peristalsis of GI via Gq GPCR
what are aboral receptors for
activate relaxation of GI via Gs GPCR
what activates oral receptors
ACh and other substances and Gq (peristalsis)
what activates aboral receptors
norepi and other substances and Gs (relaxation)
how does alteration of ACh, norepi serotonin and others with drugs impact ENS?
impacts oral and aboral receptors to either increase peristalsis (diarrhea!!) or cause GI slowing
what is NANC
nonadrenergic noncholinergic neurons
what are the NANC “players”
nitric oxide, vasoactive intestinal peptide, calcitonin gene related peptide, adenosine, CCK, endogenous opioids, tachykinins
what do NANC do
- penile erection
- peristalsis GI
- relaxation of vascular smooth muscle
action of sympathetic activation on blood vessels
a1 receptors are innervated, but B2 receptors are NOT innervated…therefore, GPCR a1 causes primary vasoconstriction then slight relaxation as the adrenal medulla releases epinephrine to activate (noninnervated) B2
action of sympathetic activation on lungs
B2 receptors (not innervated) are activated by epinephrine release by adrenal medulla, causing bronchodilation
what activates epi and norepi release from adrenal medulla?
ACh on Nn
sympathetic actions
- mydriasis (dilation)
- reduced saliva flow (a1)
- increased SV and HR (B1)
- vasoconstriction
- reduced peristalsis and secretion
- increased glucogenolysis
- inhibition of gladder contraction
- epinephrine release
- B2 bronchodilation
parasympathetic actions
- miosis (constriction) and accommodation
- stimulated saliva flow
- decreased HR (vagus)
- bronchoconstriction (vagus)
- peristalsis and secretion (vagus)
- stimulate bile release (vagus)
- bladder contraction
which effector organ is innervated by the sympathetic nervous system but is activated when postgang sympathetic nerve releases ACh?
adrenal medulla
describe somatic neuron
Ach Nm neuron (NMJ)
describe parasympathetic neuron
Ach releasing (long )preganglionic neuron at Nn, then Ach releasing (short) postganglionic fiber at Muscarinic receptor on target organ
describe sympathetic neuron
Ach releasing (short) preganglionic neuron at Nn, then norepi (mostly) releasing (long) postganglionic fiber at adrenergic receptor on target organ
except adrenal medulla, has Ach releasing neuron
how does SNS stimulate bronchodilation
works through Nn on adrenal medulla to release epi
relies on epi from adrenal medulla because B2 is not innervated
what is the autoreceptor
a2 – turns off further release of sympathetic outflow from the neuron
what is the M1 receptor
Gq receptor in head
M2 receptor
Gi receptor in heart, and autoreceptor
M3 receptor
Gq receptor everywhere else
a1 receptor
Gq coupled, increases Ca which acts on smooth muscle to contract (arterial smooth muscle, mydriasis)
a2 receptor
Gi coupled, autoreceptor, CNS, deactivates K (If) (funny current) channels (doesn’t bring back up to depolarizing)
on presynaptic terminal
B1 receptor
Gs on the heart and juxtaglomerular cells (macula densa) to increase renin
B2 receptor
Gs relaxation of smooth muscle, bronchioles, gravid uterus, vascular endothelium (epi>NE)
and skeletal muscle, increases glucose uptake and Na/K ATPase
what causes Reynaud’s syndrome
excessive a1 stimulation
B3 receptor
Gs lipolysis, thermogenesis, detrusor relaxation (step urination)
what causes contraction in gravid uterus
toward the end of pregnancy, increased number of a1 receptors in the gravid uterus cause it to contract
how does Gs inhibit platelet activation
vasodilator activated phospholipid inside of the platelet is phosphorylated by Gs, which decreases likelihood of platelet being activated and aggregate
what degrades cAMP
phosphodiesterase (PDE)
how do some indirect agonists work
inhibit PDE so longer functioning of cAMP
what is the SNS autoreceptor
a2
what is the PSNS autoreceptor
M2 and M4
presynaptic mechanism of regulation
a2 autoreceptor and M2 autoreceptors
postsynaptic mechanism of regulation
receptor down and upregulation
what occurs if receptor is constantly blocked
is upregulated
what occurs if receptor is constantly activated
is downregulated and endocytosed via phosphorylation and activation of beta arrestin
how to cause tolerance
constant exposure of drug to receptor causes downregulation of receptor.
what causes withdrawal
a sudden stoppage of a drug that has caused downregulation of receptors, causes opposite effect of the drug bc fewer receptors and took away excess agonist
what causes dependence
no longer have regular or normal function without an exogenous substance due to receptor downregulation and withdrawal
steps of beta receptor desensitization
- initial exposure to agonist causes cAMP response
- continued exposure causes diminished response within a few minutes due to phosphorylation of receptor with subsequent beta arrestin binding
- internalization of bound receptor
- dephosphorylation by phosphatase
- return to cell membrane OR lysosomal degradation
how are blood vessels controlled in PSNS
M3 receptors are NOT innervated aka no endogenous signal
therefore, a drug that increases ACh won’t impact this receptor because it can’t travel to it
how are nicotinic receptors activated
2 ACh molecules
where are M receptors found
organs innervated by PSNS and pili erector muscle and eccrine sweat glands
what is the result of activation of Nn in the ganglia?
increased outflow of both SNS and PSNS
what is the result of inhibition of acetylcholinesterase?
accumulation of ACh and increase of SNS and PSNS
what controls BP
almost entirely SNS
describe baroreceptor reflex arc
stimulation of a1 on vascular smooth muscle causes contraction and increased peripheral resistance, increasing BP. body responds by activating M2 on the heart which decreases HR.
what do drugs that cause vasoconstriction usually cause?
reflex decrease in HR
what do drugs that cause vasodilation usually cause
reflex increase in HR
what is mecamylamine used for
it is a Nn antagonist used in exams to test knowledge of reflex responses of HR to BP
MOA mecamylamine
blocks Nn, the reflex pathway is blocked at the ganglia so no reflex change in HR can occur
effect of PSNS on CNS
M1 receptors, help with memory/cognition, balances with dopamine for control of movement
effect of PSNS on eye and ciliary muscle
M3 receptors for miosis (constriction) and lacrimation, and contract for accommodation (near vision)
effect of PSNS on salivation
increased salivation (M3)
effect of PSNS on bronchiolar smooth muscle
M3 - contraction (bronchoconstriction)
effect PSNS on heart
M2 causes decreased rate
effect of PSNS on blood vessels
M3 is not innervated on vasculature, but is stimulated by exogenous agonists’ increased NO release
effect of PSNS on GI and sphincters
M3 receptors cause increased secretion and peristalsis
effect of PSNS on bladder
contract detrusor muscle (urination) (M3), trigone and sphincter relax (M2)
effect of PSNS on male GU
erection via NANC increased NO
M3
effect of SNS on CNS
beta 2 provokes fear, anxiety, mood and learning
alpha 2 increases signal to noise ratio
effect of SNS on the eye
alpha 1 causes mydriasis (dilation)
beta causes increased aqueous humor
effect of SNS on salivary
alpha 1 decreases salivary
effect of SNS on bronchiolar smooth muscle
beta 2 causes bronchodilation
effect of SNS on the heart
beta 1 increases rate, force, conduction, and automaticity
effect of SNS on blood vessels
alpha 1 causes contraction and increased blood pressure
beta 2 causes relaxation and decreased blood pressure via epi
effect of SNS on GI and sphincters
alpha 1 causes decreased secretion, and decreased peristalsis, and decreased contraction
effect of SNS on liver
alpha 1 and beta 2 cause glycogenolysis and gluconeogenesis
effect of SNS on sweat glands
M3 receptors respond to promote sweating
effect of SNS on kidney
beta 1 causes increased renin release from JGA
effect of SNS on bladder
beta 3 causes detrusor to relax
alpha 1 causes trigone and sphincter to contract
effect of SNS on male GU
alpha 1 causes ejaculation
effect of SNS on uterus
alpha 1 causes gravid contraction
beta 2 causes gravid and nongravid relaxation
effect of SNS on fat cells
beta 3 causes thermogenesiss, lipolysis, decreased leptin release
effect of SNS on skeletal muscle
beta 2 causes K and glucose uptake
MOA of nicotine
full agonist at nicotinic receptors, but at high doses is a depolarizing nicotinic antagonist (noncompetitive)
initial action of nicotine
turns on Nn receptors, but doesn’t let go = depolarizing blockade (desensitization)
why is vascular tone predominantly sympathetic
alpha 1 receptor gets the signal from neuron that releases norepi but M3 receptors on blood vessels don’t have innervation (no postganglionic fiber leads to M3) so see only sympathetic.
dominant tone of arterioles
sympathetic (alpha 1 is innervated, M3 is not)
dominant tone of veins
sympathetic
dominant tone of heart
parasympathetic (M2)
dominant tone of pupil
parasympathetic (M3)
dominant tone of ciliary
parasympathetic (M3)
dominant tone of GI
parasympathetic (M3)
dominant tone of bladder
parasympathetic (M3)
dominant tone of salivary
parasympathetic (M3)
dominant tone of sweat
sympathetic (but have M3)
what occurs with prolonged toxic levels of nicotine?
Nn receptor becomes refractory and effects will match “blockade” due to loss of dominant tone (opposite effect)
