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Subtypes of Alpha Adrenergic ReceptorsAlpha1A 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 anti-
nociceptive 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,
respectively1Intrinsic Mechanisms Produced By Receptor
ActivationMuscarinic 2 receptors: Gi/Go inhibits adenylyl cyclase,
inactivatescalcium channels, increases potassium efflux
hyperpolarizationINHIBITORY
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
cyclaseactivity in most smooth muscle cells, decrease intracellular
calciumINHIBITORY2CLASSIFICATION OF RECEPTORSAdrenergic
Receptors(all are GPCRs)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
Dr. Raymond Alquist - 19483
Ca++SarcoplasmicReticulumCa++Increased ContractionCardiac
CellCa++Depolarization of CellReceptors at Neuroeffector
JunctionInvoluntary Contraction Of Cardiac CellVoltage-gated
Channel
4Gi or o proteinadenylcyclaseATPInactive ProteinKinase AActive
ProteinKinase ACa++SarcoplasmicReticulum
Decreased Contraction or RelaxationAChM2
receptorK+HyperpolarizationinhibitscAMPInactivateschannelCardiac
CellAC open calcium channelPKA opens calcium channeland releases
Ca++ fromSR
5SarcoplasmicReticulumCalmodulinOn MyosinCalmodulin
ComplexSmooth Muscle CellMLCKMLCK*Myosin Light ChainMyosin Light
Chain PO4ActinCONTRACTIONMyosin
PhosphataseRELAXATIONCa++Ca++STIMULIATPMyosinVoltage-gatedchannel
6M3 ReceptorGq
ProteinPLCPIP2DAGIP3SarcoplasmicReticulumCa++Ca++Protein Kinase
CCalmodulinCalmodulin ComplexSmooth Muscle CellMLCKMLCK*Myosin
Light ChainMyosin Light Chain PO4ActinCONTRACTIONATPADPPO4 AChPIP2
= phosphatidyl inositol biphosphateIP3 = Inositol triphosphateDAG =
Diaacylglycerol
7
Anatomy of a Blood Vessel8Endothelial Cell Lining Blood Vessel
LumenMuscarinic
3ReceptorAcetylcholineeNOSL-ArginineL-CitrullineNitricOxidePLCPIP2IP3SarcoplasmicReticulumCa++CalmodulinCa++-Calmodulin
ComplexGq Protein
9Muscarinic 3ReceptorSarcoplasmicReticulumCa++Ca++Vascular
Smooth Muscle CellMyosin Light Chain PO4Myosin PhosphataseMyosin
Light ChainCalmodulinCalmodulin
ComplexMLCKMLCK*CONTRACTIONActinNitricOxideGTPCyclicGMPGuanylCyclasePLCinhibitsCa++RELAXATION
Myosin Light Chain
10
Effector Protein(Adenyl Cyclase)
ATPcAMPRESPONSENEGDPGDPGTP5AMPPDEG Protein-Coupled Receptor
Second Messenger ReceptorCa++Beta receptorReceptors at
Neuroeffector Junction
11Alpha1 Gq
ProteinPLCPIP2DAGIP3SarcoplasmicReticulumCa++Ca++Protein Kinase
CCalmodulinCalmodulin ComplexSmooth Muscle CellMLCKMLCK*Myosin
Light ChainMyosin Light Chain PO4ActinCONTRACTIONATPADPPO4NE
12Gi or o proteinadenylcyclaseATPCa++Alpha 2 Receptor
AgonistAlpha 2
PresynapticK+HyperpolarizationinhibitscAMPInactivateschannelDecrease
Release of NeurotransmitterPresynaptic Nerve Terminal or CNS
13
Gs proteinBeta-1ReceptoradenylcyclaseATPcAMPInactive
ProteinKinase AActive ProteinKinase
AphosphorylationCa++SarcoplasmicReticulumCa++Enhance actin
andmyosin interactionIncreased ContractionIncreased Ca++Binding to
troponinNECardiac CellCa++Ca++
14Gs
ProteinAdenylCyclaseSarcoplasmicReticulumCa++Ca++CalmodulinCalmodulin
ComplexSmooth Muscle CellMLCKMLCK*Myosin Light ChainMyosin Light
Chain PO4ActinCONTRACTIONBeta TwoReceptorATPcAMPEpi.,
AlbuterolTerbutalineact. PKaK+abnormal
phosphorylationHyperpolarizatiionRELAXATION*(inactive)
15Responses of Effector Organs to Autonomic Nerve
ImpulsesSympathetic 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.Sympathetic and Parasympathetic TONEContinually
active SNS: Blood Vessels - maintain peripheral resistance PNS:
Heart
Denervation Supersensitivity111111Loss of sympathetic
toneincrease in intrinsictone of smooth muscle16Audio Hijack Pro
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