Pharmacology DSA Flashcards
What does VMAT-2 do?
transports NE, epi, DA, and serotonin into vesicles –> release upon AP and Ca2+ influx
What does reserpine do?
blocks VMAT-2 so NE, Epi, DA, and serotonin are not put into vesicles
What does hemicholinium do?
blocks choline’s transport into a cell for synthesis
What parts of epinephrine synthesis occur in the nerve cytoplasm?
Tyrosine –> dopa –> dopamine
What parts of epinephrine synthesis occur in the vesicle?
What part is mainly in the adrenal medulla?
Dopamine –> norepinephrine –> epinephrine
norepi –> epi is in adrenal medulla
What is the effect of alpha2 receptor stimulation?
decreased insulin secretion
aggregation
decreased release of NE
vascular SM contraction
What is the effect of beta2 receptor stimulation?
smooth muscle relaxation
glycogenolysis, uptake of K+
What transports tyrosine into a nerve terminal?
Na+ - dependent tyrosine transporter
Where are M1 receptors located and what is their effect?
CNS, ganglia
Gq = activation of PLC, IP3, DAG cascade
Where are beta3 receptors found?
what is their effect?
adipose tissue
lypolysis
What does dopamine act on?
CNS and renal vascular smooth muscle
What are the 2 major enzymes that metabolize catecholamines?
what is their final product that can exit the cell?
monoamine oxidase (MAO) and COMT
final product = VMA
What does NET do?
imports NE into nerve terminal (reuptake)
How does beta1 respond to epi and NE preferentially?
Where is it located?
epi = NE
juxtaglomerular cells
heart
Where are nAChRs located?
CNS
autonomic ganglia
adrenal medulla
What would low blood pressure do to a baroreceptor?
decrease baroreceptor stim –> decrease parasympathetic and increase sympathetic
How does beta2 respond to epi and NE preferentially?
Where is it located?
epi»_space;Ne
smooth muscle (vascular, bronchial, GI, GU)
skeletal muscle
What NT is used for sweat gland stimulation?
ACh
What type of gpcr is beta1?
Gs –> increases adenylyl cyclase, cAMP, L-type Ca2+ channel openings
Where are M4 receptors located and what is their effect?
CNS
Gi = inhibit AC, decrease cAMP, activate K+ channels
What are the main parts of the body with parasympathetic innervation?
cardiac and smooth muscle
gland cells
nerve terminals
Where are muscarinic AChRs located?
CNS
autonomic ganglia
effector organs
sweat glands
What is the major mechanism of terminating actions of catecholamines?
reuptake into nerve terminals
What is acetylcholine mainly used in?
all preganglionic autonomic fibers
all pre and post ganglionic parasympathetic fibers
few postganglionic sympathetic (sweat glands)
Where are M2 receptors located and what is their effect?
heart, nerves, smooth muscle
Gi = inhibit AC, decrease cAMP production, activate K+ channels
How does alpha1 respond to epi and NE preferentially?
Where is alpha1 located?
epi greater than or equal to NE in vascular, GU SM liver intestinal smooth muscle heart
What is norepinephrine used in?
postganglionic sympathetic fibers
What is the effect of alpha1 receptor stimulation?
contraction
glycogenolysis, gluconeogenesis
hyperpolarization and relaxation
increased contractile force, arrhythmias
How is the adrenal gland stimulated to release epi and NE?
sympathetic ACh –> NAChrs –> 80% epi and 20% NE
What is the effect of Beta1 receptor stimulation?
increased renin secretion
increased force and rate of contraction and AV nodal conduction velocity
What are sympathomimetic agents?
drugs that mimic or enhance alpha and beta receptor stimulation
What type of gpcr is alpha1?
Gq
What type of gpcr is beta2?
Gs –> increases adenylyl cyclase
Where are M3 receptors located and what is their effect?
glands, smooth muscle, endothelium
Gq = activation of PLC, IP3, DAG cascade
How does alpha2 respond to epi and NE preferentially?
where is it located?
epi >/= NE pancreatic islets platelets nerve terminals vascular smooth muscle
What would high blood pressure do to a baroreceptor?
increase baroreceptor stimulation –> increase parasympathetic NS and decrease sympathetic
What is the sequence of events of epinephrine synthesis?
Tyrosine –> dopa –> dopamine –> norepinephrine –> epinephrine
Where does epinephrine synthesis occur?
adrenal medulla
in a few epinephrine-containing pathways in the brain
What are the main parts of the body with sympathetic innervation?
sweat glands
cardiac and smooth muscle, certain gland cells
renal vascular smooth muscle
Which muscarinic receptors are Gi?
M2, M4
Which muscarinic receptors are Gq?
M1, M3, M5
What is the function of nAChRs?
excitatory
release of catecholamines (in sympathetic ns?)
What is the function of muscarinic AChRs?
excitatory and inhibitory
sweat secretion
What type of gpcr is alpha2?
Gi
What does cocaine do?
inhibits NET so there is more NE hanging out in the synapse
What does DAT do?
reuptakes DA into nerve terminal
How does the parasympathetic NS achieve vasodilation?
no innervation of SM
ACh –> mAChRs on endothelial cells –> NO released –> vasodilation
Where are M5 receptors located and what is their effect?
CNS
Gq = activate PLC cascade, etc
What type of gpcr is the beta3 receptor?
How does it preferentially respond to epi and NE?
Gs
NE > Epi
