Physiology Lecture (12) PDF

Physiology Adrenergic Transmission LECTURE (12) DR. El-Sawy 0  Physiology Adrenergic Transmission  Noradr...

Physiology Adrenergic Transmission LECTURE (12) DR. El-Sawy 0  Physiology Adrenergic Transmission  Noradrenaline is chemical transmitter of sympathetic nervous system.  Noradrenaline is a member of Catecholamines. a. Adrenaline. Includes b. Noradrenaline. c. Dopamine. 1) All sympathetic postganglionic fibers except : Sweat glands. Skeletal muscle Blood vessel. Sites of 2) Adrenal Medulla: release Adrenaline (80%) Noradrenaline (40%) 3) Some Synapses in the CNS.  In liver: Hydroxylation Phenyl-alanine Tyrosine  In axoplasm of adrenergic nerve fibers: Hydroxylation Tyrosine DOPA ( Di-hydroxy phenyl-alanine) Decarboxylation Synthesis DOPA Dopamine  Dopamine is transported into vesicles into nerve ending : + OH Dopamine Noradrenaline  In SRM and CNS neurons: This reaction goes one step to form adrenaline. + CH3 Noradrenaline Adrenaline DR. El-Sawy 1  Physiology Adrenergic Transmission Note Synthesis begins in cytoplasm and completed in vesicles present in adrenergic nerve fibers. Synthesis occurs in chromaffin cells of SRM & CNS neurons. Dopamine is present in certain parts of brain ( basal ganglia ) with much higher concentration than noradrenaline.  Mainly Inside the nerve terminals in vesicles.  Some are free in cytoplasm Storage  In adrenal medulla: Adrenaline and Noradrenaline are stored in the form of granules in chromaffin cells.  When the action potential reaches the axon terminal → opens voltage-gated Ca+2 channels → Ca2+ influx→ ↑↑ Ca2+ level → move vesicles toward membrane and fuse with it → vesicles rupture and empty their content outside nerve fiber → NA cross the cleft (10-30 nm) & bind to its receptors on effector organ.  Stimulation of sympathetic preganglionic nerve fibers relaying on Release chromaffin cells in SRM causes adrenaline and NA release. DR. El-Sawy 2  Physiology Adrenergic Transmission Mechanism of action of Catecholamines :  Catecholamines binds to receptors on postsynaptic membrane it either : 1) ↑ permeability to Na and Ca → Na and Ca influx → Depolarization (stimulation ) 2) ↑ permeability to K and Cl → K efflux and Cl influx → Hyper-polarization ( inhibition) 3) Stimulation of adenyl-cyclase : → Conversion of ATP into C-AMP (initiate many intracellular activities) DR. El-Sawy 3  Physiology Adrenergic Transmission Removal of catecholamines : Neuronal uptake Extra neuronal uptake Excretion in urine Accounts for removal Account for removal of 15% Very small of 85 % Destroyed by C.O.M.T. amount Either stored or destroyed by M. A.O MOA COMT Catecholamine o- methyle Mono-amino-oxidase. transferase. Neuronal uptake. Extra -neuronal uptake. Produce oxidation Produce methylation Remove 85%. Remove 15%. Present in mitochondria of Present in all tissues especially adrenergic fibers , liver and kidney & brain kidney Definition: Receptors which respond to adrenaline and noradrenaline. Classification: α receptors β receptors β1 αI β2 α2 β3: present in adipose tissue → lipolysis. β4, 5: under research. DR. El-Sawy 4  Physiology Adrenergic Transmission Alpha Alpha Beta Beta  Postsynaptic membrane on  Pre-synaptic sympathetic nerve  Post-synaptic membrane in  Post-synaptic membrane in effector organ ending & ganglion cells effector organs as : effector organs as Smooth ms of: (auto receptors) 1) Heart. 1) Skeletal ms blood vessels Site 2) Intestine. 2) Bronchial wall  Post-synaptic membrane of 3) Kidney. 3) Bladder wall effector organ 4) Fat cells. 4) GIT wall  Activation of protein G→  Activation of protein G  Activation of protein G a. ↑Intracellular IP3 → inhibit Adenyl cyclaze enzyme → Stimulation of Adenyl cyclaze enzyme MOA b. ↑intracellular Ca → ↓ C-AMP → ↑ C-AMP  Ca & IP3 act as second messenger  Mainly Excitatory :  Mainly inhibitory :  Mainly Excitatory :  Mainly inhibitory : 1) V.C of blood vessels 1. Pre-synaptic : 1. ↑ all cardiac properties 1. Smooth muscle relaxation 2) Contraction of pilo-erector ms. -ve feedback inhibition of 2. ↑ rennin secretion Intestinal, bladder relaxation 3) Contraction of splenic capsule. more Nor-adrenaline release 3. ↑ lipolysis. Vaso-dilatation 4) Contraction of seminal vesicle & 2. Post-synaptic : 4. ↓ platelet aggregation Broncho-dilation ejaculatory duct. V.C of some vessels 2. Stimulation of liver and ms Action 5) Contraction of bladder and GIT CNS inhibition. glycogenolysis. sphincters ↓ lipolysis 3. Stimulation of insulin secretion 6) Adrenergic sweating on palm. ↓ Insulin secretion. 4. Increased blood fibrinogen  May be inhibitory : Peripheral platelet level. 1) Intestinal relaxation aggregation 2) Inhibition of insulin secretion  Adrenaline & Nor-Adrenaline  Adrenaline Agonist  Equal to both Adrenaline & Nor-Adrenaline  More sensitive to Adrenaline Sensitivity DR. El-Sawy 5