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Subtypes of Alpha Adrenergic Receptors
Alpha1A – contraction of smooth muscle – high density in prostate
gland; also found on arteries and veins
Alpha1B – most abundant type in heart (function??), may be involved
with alpha 1A in cardiac growth and structure, may be more
abundant on blood vessels as we get older; Alpha1C was
discovered and named but was later found to be the same
as alpha1B
Alpha1D – found on coronary blood vessels and aorta – importance?
Alpha2A – inhibitory autoreceptor found on presynaptic nerve endings
of sympathetic and also parasympathetic nerves; found in
CNS and stimulation associated with hypotension and antinociceptive responses
Alpha2B – on peripheral blood vessels, low density, can produce
constriction
Alpha2C – predominately inhibitory – found in adrenal medulla and on
nerve endings to inhibit release of E and dopamine, respectively
Intrinsic Mechanisms Produced By Receptor Activation
Muscarinic 2 receptors: Gi/Go – inhibits adenylyl cyclase, inactivates
calcium channels, increases potassium efflux – hyperpolarization
INHIBITORY
Muscarinic 3 receptors: Gq/11 protein – increase phopholipase C activity,
increase formation of IP3 and DAG, increase intracellular calcium
CONTRACTION (in most cells – exception – vascular smooth muscle cells)
Alpha one receptors: Gq/11 protein – same as muscarinic 3 receptor
mechanism - CONTRACTION
Alpha 2 receptors: Gi/Go protein – same as muscarinic 2 receptor
mechanism – INHIBITORY
Beta one receptors: Gs proteins – increase activity of adenylyl cyclase,
increase intracellular calcium – EXCITATORY
Beta 2 receptors: Gs proteins – increase activity of adenylyl cyclase
activity in most smooth muscle cells, decrease intracellular calcium
INHIBITORY
CLASSIFICATION OF RECEPTORS
Adrenergic Receptors
(all are GPCRs)
Dr. Raymond Alquist - 1948
Alpha one receptors – vascular and nonvascular smooth muscle,
Gq protein – contraction
Alpha two receptors – presynaptic nerve terminals, pancreatic beta cells,
vascular smooth muscle, Gi/Go protein – inhibitory most of the time
(exception on vascular smooth muscle)
Beta one receptors – heart, J-G cells within kidneys, Gs proteins –
excitatory
Beta two receptors – smooth muscle (vascular, bronchial, GI and UT),
Gs protein – inhibitory
Beta three receptors – adipose tissue, Gs protein – lipolysis
Receptors at Neuroeffector Junction
Involuntary Contraction Of Cardiac Cell
Ca++
Voltage-gated
Channel
Depolarization of Cell
Sarcoplasmic
Ca++
Reticulum
Increased Contraction
Cardiac Cell
ACh
M2 receptor
inhibits
Gi or o protein
K+
Hyperpolarization
Inactive Protein
Kinase A
Inactivates
channel
Ca++
adenyl
cyclase
ATP
cAMP
AC – open calcium channel
PKA – opens calcium channel
and releases Ca++ from
SR
Active Protein
Kinase A
Sarcoplasmic
Reticulum
Decreased Contraction or Relaxation
Cardiac Cell
STIMULI
Voltage-gated
channel
Calmodulin
On Myosin
Ca++
Ca++
Calmodulin Complex
MLCK
MLCK*
ATP
Myosin Light Chain
Myosin
Phosphatase
RELAXATION
Myosin Light Chain – PO4
Myosin
Actin
CONTRACTION
Smooth
Muscle Cell
ACh
PIP2
PLC
M3 Receptor
DAG
Ca++
IP3
Ca++
Protein Kinase C
Calmodulin
ATP
Calmodulin Complex
MLCK
Myosin Light Chain
ADP
PO4
MLCK*
Myosin Light Chain – PO4
Actin
CONTRACTION
PIP2 = phosphatidyl inositol biphosphate
IP3 = Inositol triphosphate
DAG = Diaacylglycerol
Smooth
Muscle Cell
Anatomy of a Blood Vessel
Acetylcholine
Muscarinic 3
Receptor
PIP2
PLC
IP3
L-Arginine
Ca++
Calmodulin
Ca++-Calmodulin
Complex
Nitric
Oxide
Endothelial Cell Lining Blood Vessel Lumen
L-Citrulline
Muscarinic 3
Receptor
R
E
L
A
X
A
T
I
O
N
Sarcoplasmic
Reticulum
Ca++
Ca++
Cyclic
GMP
GTP
Calmodulin
Calmodulin Complex
MLCK*
MLCK
Myosin Light Chain
Myosin Light Chain – PO4
Actin
Myosin
Phosphatase
PLC
CONTRACTION
Vascular Smooth
Muscle Cell
NE
Receptors at Neuroeffector Junction
G Protein-Coupled Receptor Second Messenger Receptor
Ca++
Effector Protein
(Adenyl Cyclase)
β
GTP
cAMP
ATP
α
GDP
Beta receptor
γ
RESPONSE
GDP
PDE
5’AMP
NE
PIP2
PLC
Alpha1
DAG
Ca++
IP3
Ca++
Protein Kinase C
Calmodulin
ATP
Calmodulin Complex
MLCK
Myosin Light Chain
ADP
PO4
MLCK*
Myosin Light Chain – PO4
Actin
CONTRACTION
Smooth
Muscle Cell
Alpha 2 Presynaptic
Alpha 2 Receptor
Agonist
Gi or o protein
K+
Hyperpolarization
inhibits
Ca++
Inactivates
channel
adenyl
cyclase
ATP
cAMP
Decrease Release of Neurotransmitter
Presynaptic Nerve Terminal or CNS
NE
Beta-1
Receptor
Gs protein
ATP
Inactive Protein
Kinase A
Ca++
Ca++
adenyl
cyclase
cAMP
Active Protein
Kinase A
Enhance actin and
myosin interaction
Sarcoplasmic
Ca++
Reticulum
Increased Ca++
Binding to troponin
Increased Contraction
Cardiac Cell
Epi., Albuterol
Terbutaline
Beta Two
Receptor
Adenyl
Cyclase
cAMP
ATP
Ca++
Ca++
Calmodulin
Calmodulin Complex
MLCK
MLCK* *(inactive)
Myosin Light Chain
K+
Myosin Light Chain – PO4
CONTRACTION
RELAXATION
Actin
Hyperpolarizatiion
Smooth
Muscle Cell
Responses of Effector Organs to Autonomic Nerve Impulses
Sympathetic and Parasympathetic TONE
Continually active – SNS: Blood Vessels - maintain peripheral resistance
PNS: Heart
Loss of sympathetic tone
increase in intrinsic
tone of smooth muscle
Denervation
Supersensitivity
α1
α1 α1
α1
α1 α1
Sympathetic or Parasympathetic stimulation of receptors can result in Excitatory Effects in
some organs but Inhibitory Effects in others!
Frequently, if sympathetic stimulation causes excitation in an organ, parasympathetic
stimulation to that same organ will result in inhibition.

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