Introduction to Autonomic Pharmacology Flashcards
list the 4 main processes ANS regulates
- smooth muscle contraction / relaxation
- ALL exocrine secretions; certain endocrine secretions
- heartbeat
- certain steps in intermediary metabolism
SNS responds to the following situations (or stresses on the body)…
- trauma
- fear
- hypoglycemia
- cold
- exercise
SNS stimulation effects on:
(1) HR, BP
(2) energy metabolism
(3) blood flow/distribution
(4) pupils
(5) bronchioles
1- inc HR, inc BP
2- inc mobilization of energy stores, glycogenolysis and fat stores
3- divert blood from skin and internal organs –> skeletal muscle and heart
4- mydriasis (pupil dilation)
5- bronchiole dilation
PSNS is important in (1) functions and having (2) towards the SNS.
(rest and digest)
1- maintain essential bodily functions: digestion, elimination of waste
2- oppose/balance SNS actions
heart is mainly under (SNS/PSNS) control
BP is mainly under (SNS/PSNS) control
Heart- PSNS (M2 AChR, Gi)
BP (vasculature, α1, Gq)- SNS
list the areas only innervated by the SNS
- adrenal medulla
- kidney
- pilomotor muscles
- sweat glands
list the neuronal fibers that release ACh
- all preganglionic efferent ANS fibers
- all PSNS postganglionic fibers
- all somatic motor fibers to skeletal muscle
list the neuronal fibers that release NE
MOST postganglionic SNS fibers (exceptions: postganglionic sweat glands ACh is released, postganglionic kidney mostly DA is released, adrenal medulla is postganglionic to release Epi./NE)
Renal vascular smooth muscle is innervated by (SNS/PSNS/both) with postganglionic fibers releasing (2)
1- SNS
2- Dopamine (mostly)
adrenal medulla is special because it is innervated by (1) and responds to (2) neurotransmitter to release (3)
1- preganglionic SNS fibers
2- ACh (AChN receptors)
3- Epi (80%), NE (20%)
sweat glands are innvervated by (SNS/PSNS/both) with postganglionic fibers releasing (2) onto (3) receptors
1- SNS
2- ACh
3- ACh-M3
all preganglionic ANS fibers release (1) to postganglionic neurons with (2) receptors
1- ACh
2- AChN(n)
list the steps for the formation and release of ACh from neuron
1a) Na+/choline CHT1 symporter on axonal membrane into cytoplasm
1b) acetyl CoA from mitochondria into cytoplasm
2) choline + acetyl CoA –> ACh via ChAT enzyme
3) ACh into vesicle via VAChT antiporter; H+ out
4) Ca++ influx stimulates ACh vesicle release at synaptic membrane
5) ACh breakdown in synapse by AChE –> acetyl CoA + choline
in the release of ACh, presynaptic membranes will have (1) receptors for ACh in order to (2)
1- M2 receptors (Gi)
2- inhibit ACh release (via Ca++, negative feedback)
Describe the following:
(1) ChAT
(2) CHT1
(3) VAChT
1- choline acetyltransferase, forms ACh from choline + acetyl CoA
2- choline transporter, axonal choline-Na+ symporter into pre-ganglionic neuron
3- vesicular ACh transporter, ACh into vesicles in exchange for H+
list the steps for NE formation and release form neuron
1) Tyr influx via System L on axonal membrane
2) Tyr -(rate-limiting)-> DOPA –> DA
3) DA into vesicle via VMAT antiporter; H+ out
4) DA –> NE w/in vesicle
5) Ca++ influx stimulates NE vesicle release into synapse
6) NE reuptake via NET, or NE diffusion away from synapse
in the release of NE, presynaptic membranes will have (1) receptors for NE in order to (2)
1- α2 adrenergic receptors (Gi)
2- inhibit NE release (via Ca++, negative feedback)
Describe the following:
(1) COMT
(2) MAO
(3) NET
(4) System L
(5) VMAT
1- catechol-O-methyltransferase for NE/Epi breakdown (mitochondria)
2- monoamine oxidase for NE/Epi. breakdown (ER)
3- norepinephrine transport, reuptake NE into presynaptic neuron
4- for Tyr influx
5- vesicular monoamine transporter, for DA into vesicles for NE conversion
AChR-N receptors come in type (1) and (2). They bind to (3) ACh molecules to allow (4) to occur. [include the locations for (1)/(2)]
1- Nm (muscle type- at skeletal NMJ)
2- Nn (neuronal type- ANS postganglionic cells, adrenal medulla, brain)
3- 2 ACh
4- Na+ influx => depolarization
(nicotinic receptors are ION channel linked)
AChR-M receptors are (1) type receptors with the following different types: (2), (3), (4). They are found on the following: (5).
1- G protein coupled receptors 2- M1 (Gq) 3- M2 (Gi) 4- M3 (Gq) 5- organs with PSNS innervation, sweat glands (SNS), some cells in CNS
activation of cardiac M2 has the following end result
(Gi- note that β/γ subunits are the direct actors, not α subunit)
K+ efflux (via K+ channel) => hyperpolarization
list the M1 locations (and functions)
(Gq)
- ganglia (depolarization)
- CNS (inc cognitive function)
- vomiting center (emesis)
list the M2 locations (and functions)
(Gi)
- heart/atria (cardiac inhibition)
- presynaptic nerve terminals (inhibits ACh release, neg. feedback)
list the M3 locations (and functions)
(Gq)
- smooth muscle (contraction)
- secretory glands (secretion)
- vascular endothelium (vasodilation, via NO on vascular smooth muscle)
describe the function of M3 on vascular endothelial cells
(uninnervated M3 receptors- Gq)
1) M3 activation => inc Ca –> activates endothelial NO synthase => NO formation
2) NO diffusion to adjacent vascular smooth muscle (vessel wall)
3) NO activates guanylyl cyclase => GTP –> cGMP
4) cGMP activates cGMP-dependent protein kinase –> phosphorylation of proteins => smooth muscle relaxation = vasodilation
describe Epi/NE binding among β-adrenergic receptors
(all Gs)
β1/β3: equal Epi/NE affinity
β2: Epi affinity»_space; NE [i.e. skeletal muscle vasculature responds well to circulating Epi.)
α1/β1 adrenergic receptors are generally found in (1)
α2/β2 adrenergic receptors are generall found in (2)
1- (Gq, Gs) adrenergic nerve terminals
2- (Gi, Gs) remote from adrenergic nerve terminals (preferential to circulating Epi)
list the β1 locations (and functions)
(Gs)
- heart (inc HR, force of contraction, AV conduction velocity)
- juxtaglomerular cells (renin release)
- adipocytes (inc lipolysis)
list the β2 locations (and functions)
(Gs)
- smooth muscle (relaxation)
- skeletal muscle (inc glycogenolysis, inc K+ uptake)
- pancreatic β-cells (inc insulin secretion, less effect than α2 dec secretion)
- pancreatic α-cells (inc glucagon secretion)
- liver (inc glycogenlysis, gluconeogenesis)
- adipocytes (inc lipolysis)
list the β3 locations (and functions)
(Gs)
adipocytes (inc lipolysis)- generally limited and unclear function
list the α1 locations (and functions)
(Gq)
- vascular smooth muscle (contraction)
- GU smooth muscle (contraction- no urination)
- liver (inc glycogenolysis, gluconeogenesis)
list the α2 locations (and functions)
(Gi)
- presynaptic terminals (inhibit NE release, neg. feedback)
- platelets (aggregation)
- adipocytes (lipolysis inhibition)
- pancreatic β-cells (dec insulin secretion- larger effect than β2 inc secretion)
- vascular smooth muscle (contraction)
DA receptors important in the ANS are (1) and (2) found in (3) which functions to (4)
1/2- D1, D5 (inc cAMP)
3- smooth muscle of renal vasculature bed
4- relaxation
vasculature (arterioles, veins) are predominant with ____ receptors
α1-adrenergic receptors (Gq)
list the areas that predominantly have M3 receptors
(Gs)
- ciliary muscle (lens focusing)
- GI tract (peristalsis)
- urinary bladder (contraction => urination)
- salivary glands (inc secretion)
- sweat glands (although SNS, inc secretion)
