Sympathetic Nervous System

Sympathetic Neurotransmitters

Epinephrine

Norepinephrine

Dopamine (precursor to Epi and norepi)A

Adreneric Receptors and subunit and placement in body

ALL 7-helix receptors GPCRs

alpha 1 - coupled to “Gq” alpha subunit

alpha 2 - coupled to “Gi” subunit

Beta 1-3 - coupled to “Gs” subunit

Differently distributed amongst organs in the body

Alpha 1 receptor mechanism

• Activates phospholipase C —> hydrolyzes PIP2 to DAG + IP3

• Releases Ca+ into cytoplasm

Alpha 2 receptor mechanism

• INHIBITS adenylyl cyclase which REDUCES cAMP levels in cytoplasm

Beta receptors mechanisms

• ACTIVATES adenylyl cyclase and INCREASES cAMP levels in cytoplasm which ACTIVATES protein kinase A

3 ways to activate adreneric receptors

1) Application of adrenergic agonists (“direct acting”)

2) elevating endogenous catecholamines (“indirect-acting agents”)

3) Both mechanisms simultaneously (“mixed action agents”)

Sympathomimetic drug activation

activates alpha 1 and beta 1-3, agonization leads to energy expending response (classic fight or flight)

Alpha 2

present on the presynapse for inhibition (prevents more release of norepinephrine) a negative feedback mechanism. AGONIST=ACTIVATES alpha 2 receptor which leads to an inhibitory affect

Alpha 1 location

• acts on blood vessels —> vasoconstrictor

• hormones: epinephrine and norepinephrine

Phenylephrine

• Alpha 1 agonist

• promotes vasoconstriction

• useful for decreasing nasal congestion

Prazosin

• Alpha 1 antagonist

• promotes vasodilation

• can be used to treat high blood pressure (acute treatment not long term)

• side effects: nasal congestion

clonidine

• alpha 2 agonist

• reduces activitiy of the sympathetic NS by inhibiting release of NE

• reduces HR and promotes vasodilation

• useful for management of hypertension

Alpha 2 location

presynaptic nerve endings

-inhibits NE resease

Beta 1 location

• heart

• increases heart rate and force of contration

dobutamine

• beta 1 agonist

• increases HR and force of contraction

• used in acute treatment of heart failure

atenolol

selective beta 1 receptor antagonist

decreses HR and force of contration

Beta 2 location

Smooth muscles (relazation) —> bronchodilation and urinaryretention

Albuterol

• beta 2 agonist

• bronchodilation

• used to treat asthma and COPD

• administered through inhalation

beta 3 receptor location

detrusor muscle of bladder

urinary retention

miravegron

beta 3 agonist

• relaxation of detrusor muscle

• increased bladder capacity

• used to treat urinary incontinence