Pharm Autonomic Nervous System Flashcards
nAChR: locations, function, agonists
ionotropic
CNS, autonomic ganglia, and adrenal medulla
excitatory and release of catecholamines
mAChR: locations, function, agonists
metabotropic
excitatory and inhibitory
CNS, autonomic ganglia effector organs (cardiac and smooth muscle, gland cells, nerve terminals)
SWEAT glands
what kind of receptors are on sweat glands, what NT causes secretion, and what division of the ANS controls it?
muscuranic receptors
ACH
sympathetic
Renal vascular smooth muscle responds to
D? ?????? that’s all there is on the slide
what kind of receptor is on the adrenal medulla?
N(n)
M(1)
CNS, Ganglia
GPCR, Gq/11
Activation of phospholipase C (PLC); IP3, DAG cascade
M(2)
heart, nerves, smooth muscle
Gi/O
inhibition of adenylyl cyclase (AC) , decrease in cAMP production, activation of K channels
M(3)
glands, smooth muscle, endothelium
Gq/11
activation of PLC, IP3, DAG cascade
M(4)
CNS
Gi/0
inhibition of AC, decrease in cAMP production, activation of K channels
M(5)
CNS
Gq/11
activation of PLC, IP3, DAG cascade
Catecholamine synthesis
rxns occurring in cytoplasm
tyrosine –> Dopa –> dopamine
Catecholamine synthesis
rxns in the vesicle,
Dopamine —> norepinephrine –> epinephrine
Catecholamine synthesis
rxns occurring in the adrenal medulla
nor –> ep
how does tyrosine get into the nerve terminal?
via Na+ dependent tyrosine transporter
VMAT-2
transports NE, Epi, DA, and serotonin into vesicles, released upon AP with Ca influx
how does NE get into the nerve terminal?
Ne transporter (NET)
DAT, imports DA into the nerve terminal
DAT
dopamine transporter
NET
norepinephrine transporter
Where does cocaine work?
prevents NE transporters from reuptaking NE
Termination of catecholamine signaling
two major reuptake transporters
no enzymatic degradation in the synapse
reuptake is the major mechanism of catecholamine termination
NET and DAT
Metabolism of catecholamines (2 main enzymes) inside nerve terminal
monoamine oxidase (MAO) catechol-O-methytransferase
Alpha(1) receptor
G protein, effectors
agonist
tissue
responses
Gq –> phospholipase C, IP3, DAG, intracellular Ca
Epi > or = to NE
Vascular, GU smooth muscle
Liver
Intestinal smooth muscle
Heart
contraction, glycogenolysis, gluconeogensis
hyperpolarization, relaxation,
increased contractile force
arrhythmias
Alpha(2) receptor
G protein, effectors
agonist
tissue
responses
Gi, Go: decreases adenylyl cyclase, cAMP
Epi> NE or = to NE
Pancreatic islets (beta cells)
platelets
nerve terminals
vascular smooth muscle
decreased insulin secretion
aggregation
decreased release of NE
contraction
Beta (1) receptor
Gs
increases adenyly cyclase, cAMP, L type Ca channel openings
Isoproterenol > Epi > or = NE
juxtaglomerular cells
heart
increased renin secretion
increased force and rate of contraction and AV nodal conduction velocity
Beta (2) receptor
Gs
increases adenyly cyclase, cAMP, L type Ca channel openings
Isoproterenol > Epi»_space;> NE
Smooth muscle (vascular, bronchial, GI, GU) Skeletal muscle
RELAXATION
glycogenolysis, uptake of K
Beta (3) receptor
Gs
adenyly cyclase increase
Iso = NE > Epi
adipose tissue
lipolysis
Primary tissue locations for adrenergic receptor subtypes (from slide with pictures)
alpha1 alpha2 beta1 beta2 beta3
alpha1: smooth muscle
alpha2: presynaptic neurons, postsynaptic tissue (ocular, adipose, intestinal, hepatic, renal, endocrine, blood platelets)
beta1: heart
beta2: bronchial, uterine, vascular smooth muscle relaxation
beta3: lipolysis of adipose tissue
Rules of thumb for smooth muscle and autonomic receptors
alpha-1 receptors: stimulates contraction of all smooth muscle AND causes vasoconstriction
Beta-2 receptors: relaxes smooth muscle: VASODILATION
Muscarinic receptors: contract smooth muscle, alh
are nAChR or mAChR’s found on the smooth muscle of blood vessels?
no. neither.
Parasympathetics:
do they innervate smooth muscle of blood vessels or the blood vessels themselves?
the blood vessels themselves; no innervation of vascular smooth muscle via parasympathetics
there are mAChRs on the epithelia which ACH released via parasympathetics.
how do parasympathetics cause vasodilation?
they stimulate epithelia (not muscle) via mAChR receptors to produce NO
NO = endothelium derived relaxing factor
can be released due to mechanical stress or ACH stimu
blood pressure goes down —> ___ baroreceptors —> __ Nervous system —> __ nervous system
increases pressure on baroreceptors, causing an increase in parasympathetic activity, decreasing sympathetic activity
blood pressure goes down —> ___ baroreceptors —> __ Nervous system —> __ nervous system
decrease baroreceptor response, decrease in parasympathetic stimulation, excitation of sympathetics
three stimulants of vascular endothelia that result in NO release
Bradykinin
ACH stimulation of M receptors
shear force
Arginine is oxidized to citrulline, and NO is released, which diffuses to smooth muscle anf acts on the GTP —> cGMP system causing vasodilation
