Physiology Lecture 7 PDF

Lecture 7 Chemical transmitters of autonomic nervous system and autonomic receptors Dr. M. Abdelmohsen Assistant Professor of Physiology MBBCh, MSc, DMSc, DHPE Faculty of Medicine...

Lecture 7 Chemical transmitters of autonomic nervous system and autonomic receptors Dr. M. Abdelmohsen Assistant Professor of Physiology MBBCh, MSc, DMSc, DHPE Faculty of Medicine 2024-2025  Objectives ❖ At the end of this lecture, the first year student should be able to: Recognize the chemical neurotransmitters of autonomic nervous system and distinguish the distribution of adrenergic and cholinergic receptors all over the body.. ▪ Reference Text Book: Guyton & Hall physiology text book  Autonomic Neurotransmitters ▪ The primary neurotransmitters of the ANS are acetylcholine "Ach" and norepinephrine "NE”. Figure 8: Autonomic neurotransmitters  (1) Acetylcholine Site of release: cholinergic fibers All preganglionic neurons in both sympathetic and parasympathetic. Almost all postganglionic parasympathetic neurons. Some postganglionic sympathetic neurons e.g., sweat glands, piloerector muscles of hairs, and few blood vessels e.g., of skeletal muscle. Synthesis and storage: ▪ Cholinergic fibers have bulbous enlargements called varicosities. ▪ Ach vesicles are synthesized and stored inside these varicosities. ▪ Varicosities have large numbers of mitochondria that supply ATP required to energize Ach synthesis.  (1) Acetylcholine Secretion and fate: ▪ Depolarization of the cholinergic fibers → increases the permeability to Ca++ → Ca++ diffuse into the nerve terminals or nerve varicosities. → secretion of Ach to the exterior → persists in the tissue for a few seconds to performs its nerve signal transmitter function → Then it is split into acetate and choline by acetylcholinesterase enzyme. ▪ Choline is transported back into the terminal nerve ending, where it is used again and again for synthesis of new Ach. Cholinesterase enzyme: 2 types: 1. True cholinesterase (specific for Ach). 2. Pseudo cholinesterase (acts on choline esters e.g., succinyl choline in blood).  (2) Norepinephrine Site of release: adrenergic fibers ▪ Most postganglionic sympathetic are adrenergic except those supplying sweat glands, piloerector muscles of hairs, and few blood vessels e.g., of skeletal muscle. Synthesis and storage: ▪ As Ach, also NE vesicles are synthesized and stored inside varicosities which also contains large numbers of mitochondria to supply ATP required to energize NE synthesis with the following steps: 1) Tyrosine (by hydroxylation) →Dopa 2) Dopa (by decarboxylation) → Dopamine 3) Transport of dopamine into the vesicles 4) Dopamine (by hydroxylation) →NE 5) NE (by methylation) →Epinephrine N.B.: In the adrenal medulla about 80 % of NE converted into epinephrine.  (2) Norepinephrine Secretion and fate: a) NE Secreted by adrenergic fibers: ✓ By depolarization in the same way like cholinergic fibers → in a tissue it remains active for only a few seconds → then it is removed from the secretory site in 3 ways: 1. Reuptake into the adrenergic nerve endings: (50 – 80 %) by active transport. 2. Released into body fluids and blood (majority of the remaining NE) by diffusion. 3.Destruction (small amounts) by: MAO" in nerve endings, and COMT in all tissues. b) NE and epinephrine secreted by adrenal medullae: ✓ Remain very active for 10 to 30 seconds until they diffuse to tissue (mainly liver) where they can be destroyed by COMT. ✓ Their activity declines to the minimum after 1 to several minutes.  Autonomic receptors on the effector organs Mechanism of receptors action: Binding of transmitter with the receptor → conformational change in the structure of the protein molecule → excites or inhibits the cell by: 1. Changing permeability to one or more ions: (mainly depolarization). 2. Activating or inactivating an interior enzyme attached to the receptor protein (Second messenger formation): mainly cAMP. Conclusion Autonomic transmitter can cause inhibition in some organs or excitation in others. determined by: - Nature of the receptor protein. - Effect of receptor binding on conformational state.  Cholinergic receptors Receptor Tissue Response Mechanisms Nicotinic Skeletal Depolarization, Ach opens cation muscle producing action channel in receptor. potentials and muscle contraction. Nicotinic Autonomic Depolarization, ACh opens cation ganglia causing activation channel in receptor. of postganglionic Neurons. Muscarinic Smooth Depolarization and ACh activates G- (M3, M5) muscle, contraction of protein coupled glands smooth muscle, receptor, opening secretion of glands. Ca++ channels and increasing cytosolic Ca++ Muscarinic Heart Hyperpolarization, ACh activates G- (M2) slowing rate of protein coupled spontaneous receptor, opening depolarization. K+ channels.  Cholinergic receptors Clinical application: 1) Myasthenia Gravis: Definition: easy fatiguability of muscles. Cause: Autoimmune disease affects neuromuscular junction. Pathophysiology: antibodies block and destroy Ach receptors on the muscles → Ach can not attach to receptors → muscle is less able to contract. Symptoms: muscle weakness which gets worse with activity and improves with rest. Ptosis, difficulty in swallowing, slurred speech, limbs weakness, and chest muscles weakness (may lead to myasthenic crisis if sever). Treatment: Therapeutically: by anticholinesterase drugs Surgical: by thymectomy (removal of thymus which is the site for antibodies formation). 2) Usage of specific drugs therapeutically: ✓ To stimulate or block one of receptor’s types.  Adrenergic receptors Organ Adrenergic Receptor Adrenergic Effects (Sympatho-adrenal) Eye α1 Contraction of radial fibers of the iris dilates the pupils Heart β1 primarily Increase in heart rate and contraction strength Skin and α1 Arterioles constrict due to visceral vessels smooth muscle contraction α1 Arterioles constrict due to Skeletal muscle sympathetic nerve activity vessels β2 Arterioles dilate due to hormone epinephrine Lungs β2 Bronchioles (airways) dilate due to smooth muscle relaxation Stomach and α1 Contraction of sphincters intestine slows passage of food Liver α1 & β2 Glycogenolysis and secretion of glucose  Important Notes Norepinephrine excites → alpha receptors more than beta receptors. Epinephrine hormone excites → both types equally.  Higher nervous control of Autonomic Functions 1) Cerebral cortex: ✓ Thoughts can produce autonomic effects. 2) Hypothalamus: the most important controller of ANS: ✓ it has nuclei (centers): ✓ Posterior hypothalamus for controlling sympathetic system. ✓ Anterior hypothalamus for controlling parasympathetic system. 3) Reticular formation: ✓ It is present in the brain stem (Pons & Medulla). ✓ Acts as relay stations from the hypothalamus. 4) Spinal cord: ✓ Mainly control the defecation and micturition reflexes without involvement of the brain.  Thank You Faculty of Medicine 2024-2025