Lecture 9 Outline: Adrenal Medulla and Sympathetic Nervous System

 

I.          Background

 

A.        Adrenal medulla is made of chromaffin cells

1.         Modified post-ganglionic sympathetic neurons

            a.         Derived from neuroecotoderm

2.         Types of chromaffin cells

            a.         Adrenaline (A) storing cells

                        i.          Epinephrine

            b.         Noradrenoline (N) storing cells

                        ii.         Norepinephrine

3.         Catecholamines are stored in granules

            a.         Released upon the activation of the sympathetic NS

4.         Ratio of A and N cells determines composition of medullary secretions

            a.         For humans, there are significantly more A types

                        i.          Epinephrine is the primary hormone released when the adrenal medulla is activated

 

II.        Overview of the Autonomic Nervous System

 

A.        Somatic Nervous System

1.         Voluntary

a.         Voluntary muscle movement

2.         Sensory information to the CNS

3.         Organization of cell bodies

a.         Lie within spinal cord or brainstem

b.         Targets are controlled monosynaptically

 

B.        Autonomic Nervous System

1.         Involuntary

a.         Autonomic functions are carried out without conscious, voluntary control

2.         Cell bodies of all lower autonomic motor neurons lie outside the CNS

a.         Autonomic ganglia

b.         Neurons are postganglionic

c.         Driven by preganglionic neurons whose cell bodies are in the spinal cord or brainstem

3.         Divisions

            a.         Sympathetic

b.         Parasympathetic

4.         Divisions differ based on:

            a.         Neurotransmitter type

            b.         Fiber length

            c.         Location of ganglia

            d.         Function

 

5.         Neurotransmitter

 

Division

Preganglionic

Postganglionic

Sympathetic

ACh

NE

Parasympathetic

ACh

ACh

           

a.         ACh acts locally

            i.          ACh always has a stimulatory effect

b.         NE has spreads far and can exert its effects over long distances when circulated in the blood

c.         Adrenergic receptors

            i.          Alpha—stimulatory

            ii.         Beta—inhibitory (except in the heart when it is excitatory)

6.         Fiber length

            a.         Parasympathetic

                        i.          Long preganglionic

                        ii.         Short postganglionic

            b.         Sympathetic

                        i.          Short preganglionic

                        ii.         Long postganglionic

7.         Location of ganglion

            a.         Parasympathetic

                        i.          Ganglion is located in visceral organ

            b.         Sympathetic

                        i.          Ganglia lie close to spinal cord

                        ii.         Sympathetic chain ganglia

8.         Function

            a.         Divisions work in concert

            b.         Parasympathetic division

                        i.          Maintenance of function

                        ii.         Energy conservation

            c.         Sympathetic division

                        i.          Emergence

                        ii.         Intense muscular activity

9.         Sympathetic response

a.         Pupil dilated

b.         Secretory responses inhibited

c.         Stimulates sweating

d.         Heart function

i.          Increases rate

ii.         Dilates coronary vessels

e.         Increased blood pressure

            i.          Constricts most vessels

f.          Bronchioles dilate

g.         Decreased activity of digestive system

h.         Piloerection

i.          Increase metabolic rate

            i.          Glucose is released into blood

            ii.         Lipolysis

j.          Increased alertness

            h.         Causes ejaculation (vaginal reverse peristalsis)

10.       Parasympathetic response

            a.         Pupils constrict

            b.         Stimulates secretory activity

                        i.          Salivation

            c.         Heart function

                        i.          Decreases rate

                        ii.         Constricts coronary vessels

            d.         Constricts bronchioles

            e.         Increases activity of digestive system

            f.          Causes erection (penis and clitoris)

                        i.          Vasodilation

 

III.       Chemistry and Synthesis

 

A.        Synthesis

1.         Epinephrine and norepinephrine are derived from tyrosine

2.         Tyrosine is transported into cells

3.         Tyrosine is sequentially modified to form epinephrine

 

 

 

            a.         Hydroxylation at C-3 on phenyl ring

                        i.          Tyrosine hydroxylase tyrosine to DOPA

                        ii.         Formation of DOPA is the rate limiting step

            b.         Side chain decarboxylation

                        i.          Dopamine is the product

            c.         Side chain hydroxylation       

                        i.          Norepinephrine is the product

            d.         Side chain N-methylation

                        i.          Epinephrine is the product

 

4.         Catecholamines are stored in secretory vesicles

            a.         Complexed with ATP and chromogranin

5.         Secretory vesicles are released in response to stimulation

            a.         Ca2+ dependent exocytosis

 

B.        Metabolic inactivation

1.         COMT—catechol-amine-O-methylase

            a.         Extracellular

            b.         Reduces concentration of catecholamines in synapse

                        i.          Effects mediated by catecholamines are decreased

2.         MAO—monoamine oxidase

            a.         Intracellular

            b.         Reduces concentration of catecholamines in cells

                        i.          Decreases exocytosis of NE and E

                        ii.         Reduces quantal content

 

IV.       Receptors for Sympathoadrenal and Parasympathetic Systems

 

A.        Types of receptors

1.         Adrenergic receptors mediate effects of sympathetic and adrenal medulla

2.         Cholinergic mediate the effects of the parasympathetic system

 

B.        Types of cholinergic receptors

1.         Nicotinic receptors

            a.         Blocked by curare

            b.         Found at neuromuscular junction

                        i.          Activation of skeletal muscle

            c.         Found at innervation between post-ganglionic parasympathetic neuron and its target

2.         Muscarinic receptors

            a.         Blocked by atropine

            b.         Found at effector cells such as smooth muscle

 

C.        Types of adrenergic receptors

1.         Alpha (a)

2.         Beta (b)

 

D.        Adrenergic receptors differ in their ability to bind NE and E

1.         Potency for a-AR’s

            a.         E > NE > ISO

                        i.          Isoproterenol (ISO) is a synthetic catecholamine

                        ii.         Stimulates both beta1 and beta2 adrenergic receptors

                        iii.        Does not activate alpha receptors

2.         Potency for B-AR’s

            a.         ISO > E > NE

 

3.         Types of alpha receptors

            a.         a1 and a2

4.         Generalized effect of activation of alpha receptors is vasoconstriction

            a.         a1 require SNS activation

                        i.          Synaptic release of NE—neuronal

                        ii.         Binds E > NE

            b.         a2 require exogenous catecholamines

                        i.          Adrenal medullary release of NE and E—hormonal

                        ii.         Binds E > NE

 

5.         Types of beta receptors

            a.         B1, B2 and B3

6.         Effects of B1

            a.         Lipolysis of adipose

            b.         Contraction of cardiac muscle

            c.         Binds E and NE equally

7.         Effects of B2

            a.         Bronchial dilation

            b.         Vasodepression

            c.         Binds E > NE

8.         Effects of B3

            a.         Lipolysis of adipose

            b.         Binds NE > E

 

E.         Transduction mechanisms

1.         a1 activate PIP

            a.         IP3 and DAG increase intracellular Ca2+

            b.         ­Ca2+ initiates signaling cascades that result in cellular response

2.         a2 inactivate adenylate cyclase

            a.         Decreased levels of cAMP

3.         b-AR’s activate adenylate cyclase

            a.         Increased levels of cAMP activate hormone sensitive enzymes

 

Receptor

Effectively Binds

Effect of Ligand Binding

Actions

Alpha1

Epinephrine, Norepinphrine

Increased free calcium

Smooth muscle contraction

Alpha2

Epinephrine, Norepinphrine

Decreased cyclic AMP

Smooth muscle contraction

Beta1

Epinephrine, Norepinphrine

Increased cyclic AMP

Heart muscle contraction

Beta2

Epinephrine

 

Increased cyclic AMP

Smooth muscle relaxation

Beta3

Norepinephrine

Increased cyclic AMP

Lipolysis

 

 

V.        Functions of the Sympathoadrenal System

 

A.        Maintenance of homeostasis

1.         ¯BP, blood glucose or O2 activate the sympathetic NS and adrenal medulla

 

B.        Response to stress

1.         Events that alter homeostasis activate the sympathetic NS and adrenal medulla

            a.         Internal or external events

            b.         Real or perceived “threats”

2.         NE is released by sympathetic NS

3.         E is released by the adrenal medulla

 

C.        Nature of effect is determined by receptors

1.         Effector cells may have:

            a.         a and b receptors

            b.         b and cholinergic receptors

2.         Smooth muscle contraction is regulated through a receptors

            a.         Not in the intestines

3.         Smooth muscle relaxation is regulated through b receptors

            a.         Not cardiac muscle

4.         When both a and b receptors are present, a masks the effects of b receptors

5.         Cellular secretion

            a.         b receptors cause secretion

            b.         a receptors inhibit secretion

6.         When b receptors control relaxation, cholinergic regulate contraction

 

VI.       Physiological Effects of the Sympathoadrenal System

 

A.        Effects on carbohydrate metabolism

1.         Glucose is needed when stressed

            a.         E → ­hepatic glycogenolysis

                        i.          Mediated by b receptors

            b.         E → activation of skeletal muscle glycolytic pathways

                        i.          Lactic acid

            c.         Lactic acid is converted to glucose in the liver

                        i.          E → gluconeogenesis

            d.         NE + E → ¯ pancreatic insulin secretion

                        i.          Mediated by a receptors on B cells

                        ii.         Reduces glucose entering cells (­BG)

            e.         NE + E → ­ pancreatic glucagon secretion

                        i.          Mediated by b receptors on A cells

                        ii.         Glycogen is degraded (­BG)

 

B.        Effects on fat metabolism

1.         Adipose has b receptors (1 & 3)

            a.         NE + E → lipolysis

            b.         E → ­cAMP activation of lipases → ­FA

                        i.          FA’s can be used directly by the brain and heart

                        ii.         FA’s can be converted to glucose by the liver

 

C.        Effects on protein metabolism

1.         E → ¯ release of amino acids from skeletal muscles

            a.         Suppression of proteolysis is mediated by b receptors

 

D.        Cardiovascular response to stress

1.         E → ­ rate and force of cardiac muscle contraction

            a.         Mediated by b receptors

                        i.          Only involuntary muscle controlled by b receptors

 

E.         Dilation of bronchioles

1.         NE + E → dilation of smooth muscle of bronchioles

            a.         Mediated by b receptors