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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

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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

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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

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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 v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5Audio Hijack Pro v2.10.5