1. Autonomic Nervous System (ANS) Cholinergic Drugs 1 أ 0 م 0 د. وحدة بشير اليوزبكي

2. Objectives At end of this lecture, the students should be able to: 1- Identify some facts about the anatomical and physiological division of Autonomic Nervous System (ANS). 2- List the neurotransmitters of ANS, concentrating mainly on that of parasympathetic nervous system (PSNS) (Types, synthesis & inactivation). 3- Enumerate the receptors of PSNS (types, locations). In a way, consistence with standards scientific curriculum

3. Autonomic Nervous System (ANS) ANS: It is the major involuntary, unconscious, autonomic portion of the nervous system. General Organization: The ANS consists of two main parts: 1- Central ANS. 2- Peripheral ANS, which consists of : a- Parasympathetic (PSNS). b- Sympathetic (SNS).

4. Central Autonomic Nervous System - The head of the ANS is the hypothalamus. contains many nuclei of which located posterolaterally (Symp.) & anteromedially (PS). - It receives its input from: 1- Somatic & visceral afferent fibers. 2- Pituitary (hypophysis). 3- Limbic system. 4- Thalamocortical system & brainstem. 5- Internal location from receptors sensitive to Temp, ionic conc. (osmolarity) & hormone concentration.

5. Peripheral Efferent Parts of ANS - Classically the Peripheral ANS has been considered to be exclusively efferent. - The efferent pathway of ANS, (both S & PS division) transmit impulses from central connection (hypothalamus) to the effecter cells.

6. Efferent Neuron of ANS - Both divisions of ANS (PS & S) consist of preganglionic & postganglionic neurons. - The preganglionic neuron arises from cells of central origin & ends at the ganglion. - The postganglionic neurons consist of fibers arise from cell bodies within the ganglion, that pass to the effecter organ.

7. Para sympathetic Nervous System (PSNS) Spinal Roots of Origin: - The parasympathetic preganglionic motor fibers originate in the cranial nerve nuclei (III,VII,IX,X) & the sacral segment (S2-S4) of the spinal cord (craniosacral).

8. Location of the PS Ganglia - Most PS ganglia located faraway in the organs innervated, more distant from the spinal cord. Length of pre & post ganglionic fibers: - Because of the location of the ganglia: The preganglionic fibers of PSNS are long & the post ganglionic fibers are short.

9. Neurotransmitters of ANS Neurotransmitters: The chemical substances which mediate the transmission of nerve impulse between different parts of nervous system. 2 Types in ANS: 1- PSNS: Acetylcholine. 2- SNS: Nor epinephrine (Nor adrenaline) & Epinephrine (Adrenaline).

10. Neurotransmission at PSNS (cholinergic) neuron (Synthesis & Release of Ach)

11. Neurotransmission at cholinergic neuron (Synthesis & release of Ach) - These involves six steps: 1. Synthesis of acetylcholine: choline is transported from the ECF into cholinergic neuron. - Choline acetyltransferase (CAT) enzyme catalyzes the reaction between choline and acetyl Co A to form acetylcholine. Notes: - Choline transport is the rate limiting steps. - CAT is the cytosolic enzyme found only in cholinergic neuron.

12. Synthesis & Release of Ach 2. Storage of acetylcholine in vesicles: the Ach. is packaged into vesicles by active process. 3. Release of Ach: - When action potential arrives at the nerve ending, the sensitive calcium channel in the presynaptic membrane open & cause increase in the concentration of intracellular calcium, this promote the fusion of the vesicle with the cell membrane and release of Ach into the synapse.

13. Synthesis & Release of Ach 4. Binding to receptor : - Ach that released from the synaptic vesicle diffuse across synaptic space and bind to post synaptic receptors of target cell. - Binding to the receptor lead to the biological response within the cell such as: a- Initiation of nerve impulse in postganglionic fibers - The transmitter mediated depolarization is called an end plate potential (EPP) in the skeletal muscle. b- or activation of specific enzyme in the effecter cells.

14. Synthesis & release of Ach 5. Degradation of Ach: Esterase enzyme cleaves Ach to choline & acetate This occur in the synaptic cleft. Note: Ach hydrolyzed within about 1ms by Ach esterase enzyme, so a presynaptic AP produces only one postsynaptic AP. 6. Recycling of choline : - After Ach hydrolyzed more than 50% of this choline is normally recaptured by the nerve terminal back into the neuron where it is acetylated and stored.

15. Cholinergic Receptors (Cholinoceptors) -These receptors respond to Ach & its analogues. -These receptors are subdivided as follows: 1. Muscarinic receptors: MR 2. Nicotinic receptors: NR

16. Muscarinic Receptors: MR - These receptors respond to muscarins as well as Ach. - 5 types (M1, M2,M3,M4,M5), 3 well recognized: M1 (Neuronal): Nerve endings (peripheral nerve) mainly & CNS. Note: M1 also found at gastric parietal cells. -Deficiency of M1 effects in brain dementia. -Deficiency of M1 effects in brain dementia. M2 (cardiac): Heart & some nerve endings. M3 (Glandular): sm.m, glands & endothelium.

17. Locations of Muscarinic Receptors: MR 1. Postganglionic neurons of PSNS (N ending, heart, glands, sm.m). 2. Postganglionic cholinergic neurons of sympathetic nervous system (sweat glands). 3- Non innervated receptors on blood vessels. 4. In CNS. 4. In CNS.

18. Locations of Muscarinic Receptors: MR 1. Postganglionic neurons of PSNS (N ending, heart, glands, sm.m). 2. Postganglionic cholinergic neurons of sympathetic nervous system (sweat glands). 3- Non innervated receptors on blood vessels. 4. In CNS. 4. In CNS.

19. Nicotinic Receptors: NR Nicotinic Receptors: NR - These receptors respond to nicotine as well as Ach. 2 major subtypes: NN: in autonomic ganglia. NM: NM endplate (N-M junction).

20. Locations of Nicotinic Receptors: NR Nicotinic receptors: NR 1. Autonomic ganglia: Synapse between preganglion and postganglionic neuron of SNS & PSNS. 2. Motor endplates at skeletal (striated) muscle at the neuromuscular junction (somatic nerve i.e. to voluntary muscle). 3- Secretion of adrenaline from adrenal medulla. 4. In CNS.

21. Neurotransmitters & Receptors of ANS