Autonomic Pharmacology Introduction

Front 1

Ach is released by these neurons:

Back 1

-Presynaptic ANS neurons
-Postsynaptic cholinergic neurons
-Postsynaptic "sympathetic cholinergic" neurons innervating sweat glands

Front 2

Types of Ach receptors and location

Back 2

-Nicotinic (Nn) on postsynaptic (prejunctional) neurons
-Nicotinic (Nm) on neuromuscular junctions
-Muscarinic (M) on cholinergic-innervated effector cells, endothelial cells of blood vessels

Front 3

NE is released by these neurons:

Back 3

Postsynaptic (prejunctional) sympathetic neurons

Front 4

Types of NE receptors and location

Back 4

-Alpha 1 and 2, Beta 1
located on effector cells innervated by adrenergic neurons
-Alpha 2
located on the terminal region of sympathetic postganglionic neurons (for negative feedback inhibition of NE)

Front 5

EPI is released by

Back 5

Adrenal chromaffin cells

Front 6

EPI receptors and location

Back 6

Alpha 1, Beta 1 and 2
located on many effector cells (released into bloodstream)

Front 7

What is a sympathetic cholinergic neuron?

Back 7

Anatomically sympathetic neuron releasing Ach to receptors on sweat glands

Front 8

What neurotransmitters are released by postganglionic sympathetic neurons?

Back 8

Norepinephrine (NE)
Dopamine (DA)

Front 9

What do dopaminergic sympathetic neurons innervate and what is their main function?

Back 9

Dopaminergic sympathetic neurons innervate the kidney and regulate renal blood flow

Front 10

What do nonadrenergic, noncholinergic (NANC) neurons release and what is thought to be their function?

Back 10

-Release ATP and neuropeptide Y, vasoactive intestinal peptide (VIP), nitric oxide (NO), and monoxide (CO)
-Contribute to overall effects of sympathetic innervation - relax smooth muscle surrounding "tubes"

Front 11

What is the general function of the autonomic nervous system?

Back 11

Regulate involuntary processes such as:
-blood pressure
-gastrointestinal motility and secretions
-airway resistance
-glandular secretions

Front 12

How does the autonomic nervous system accomplish its function?

Back 12

-Varies the frequency of action potentials in neurons
-Concentration of neurotransmitters at synaptic cleft is always mixed since different types of neurons are usually innervating
-Production of more of one type of neurotransmitter tips the balance one way which has a certain effect on the innervated cell

Front 13

8 Steps of Impulse Transmission

Back 13

1) Signal originates in CNS, emerges through preganglionic neurons terminating in ganglia

2) Axons of these neurons form synapses with dendrites/cell bodies of postsynaptic neurons

3) Variations in action potential frequency in preganglionic neurons determine its rate of Ach release into the synaptic cleft

4) Ach in the cleft binds to Nn receptors on the postganglionic neuron

5) This receptor activation determines the AP frequency of the postganglionic neuron

6) AP frequency determines the rate of neurotransmitter release at the terminus of the postganglionic neuron into its NEJ

7) Ach released into the NEJ activates M receptors on the cell surface

8) Activation of M receptors and their associated signals regulates their function

Front 14

Where and how is Ach synthesized?

Back 14

-Terminus of cholinergic neuron
-Ach is synthesized from acetyl CoA and choline by choline acetyltransferase (CAT)

Front 15

How is Ach released at the end of cholinergic neurons?

Back 15

-Higher AP frequency --> higher intracellular Ca2+ levels
-Higher Ca2+ --> higher rate of Ach packaging and release

Front 16

What happens to Ach when it is released

Back 16

Either:
-Binds to Nn, Nm, M receptors on postsynaptic cell
-Degraded by AChE into choline and acetate
-Choline and Acetate are taken back into the neuron by choline reuptake transporter (CRT), a Na+ symporter

Front 17

What are ways to increase Ach in the cleft?

Back 17

-Increase AP frequency of presynaptic neuron
-Inhibit AChE

Front 18

Where would a cholinergic neuroeffector junction be and what type of receptor would be on the postsynaptic cell?

Back 18

-Surface of an effector cell innervated by the PNS (secretory glands, bronchiolar smooth muscle, etc)
-Sweat glands

-Muscarinic receptor

Front 19

What are the two different signal pathways that can be activated by ACh via M receptors?

What do these responses depend on?

Back 19

-G protein pathway initiated (either Gaq: increased PLC/DAG/IP3 or Gai: decreased AC/cAMP)
-Beta-gamma subunit opens K+ channel, hyperpolarizing cell and slowing APs

-Responses depend on cell type

Front 20

Nicotinic receptors:
Where located?
What form do they usually take?
What is their mode of action?
What overall effect does this lead to?

Back 20

-Postganglionic PNS neurons (Nn) and muscle cells (Nm)
-Na+ channels
-ACh allows the entry of Na+, which partially depolarizes the neuron and causes fast Na+ channels to open, increasing AP frequency
-Neurons: Enhanced transmitter release downstream
Skeletal muscle: Greater twitch frequency
Smooth muscle: Greater sustained tonic contraction

Front 21

What neurotransmitters do each type of sympathetic neuron release?

Back 21

-Most - NE
-Sympathetic cholinergic - ACh
-Dopaminergic - DA

Front 22

What is the common precursor for DA, EPI and NE?

Back 22

Tyrosine

Front 23

Conversion of Tyrosine to DA

Back 23

-Tyrosine hydroxylase (TH) converts tyrosine to dopa
-Aromatic L-amino acid decarboxylase (AADC) converts dopa to dopamine

Front 24

Conversion of dopamine to NE
Where does this take place?

Back 24

-Dopamine is taken up into secretory granule by vanillyl mandelic acid transporter (VAMT)
-Dopamine beta-hydroxylase (DBH) converts DA to NE

Adrenergic postganglionic neurons

Front 25

Conversion of NE to EPI
Where does this take place?

Back 25

-NE exits the granule and is methylated by Phenyethanolamine-N-methyltransferase (PNMT)
-Re-enters granule

Takes place ONLY in adrenal chromaffin cells

Front 26

What happens to NE after it is released?

Back 26

-Binds to receptor on effector cell
-Broken down by catechol-O-methyltransferase (COMT) into normetanephrine
-Taken back into the neuron by norepinephrine reuptake transporter (NRT)
-Once taken back up by NRT, some NE is metabolized into DOPGAL by monoamine oxidase (MAO)
-Binds to alpha-2 transporters on the neuron and inhibits release of more NE