Chemical mediators and the autonomic nervous system

1. Chemical mediators and the autonomic nervous system Lecture 7

2. Learning outcome: The peripheral nervous system Basic anatomy and physiology of the ANS Transmitters in the ANS Presynaptic modulation Postsynaptic modulation Transmitters other than Acetylcholine and Noradrenalin Co-transmission Termination of transmitter action Basic steps in neurochemical transmission: sites of drug action

3. The peripheral nervous system The peripheral nervous system consists of the following principal elements: • autonomic nervous system, which includes the enteric nervous system • somatic efferent nerves, innervating skeletal muscle • somatic and visceral afferent nerves.

4. Basic Anatomy and physiology of the autonomic nervous system The ANS consists of three main anatomical divisions, sympathetic and parasympathetic and the enteric nervous system. The enteric nervous system consists of the intrinsic nerve plexuses of the GI tract, which are closely interconnected with the sympathetic and parasympathetic system. The ANS conveys all of the outputs from the central nervous system (CNS) to the rest of the body except for motor innervation of skeletal muscle. The enteric nervous system has sufficient integrative capabilities to allow it to function independently of the CNS.

5. But the sympathetic and parasympathetic system are agents of the CNS, and can not function without it. The ANS is largely outside the influence of voluntary control. The main processes that it regulates are: • contraction and relaxation of smooth muscle • all exocrine and certain endocrine secretions • the heartbeat • energy metabolism, particularly in the liver and skeletal muscle

7. The main difference between the autonomic and the somatic efferent pathways is that the former consists of two neurons arrange in series, whereas in the latter a single motoneuron connects the CNS to the skeletal muscle fiber. The two neurons in the autonomic pathway are known , respectively, as preganglionic and postganglionic. Basic (two neuron) pattern of the sympathetic and parasympathetic system consists of preganglionic neurons with cell bodies in the CNS and postganglionic neurons with cell bodies in the autonomic ganglion

9. Parasympathetic system is connected to the CNS via : -cranial nerve outflow (iii, vii, ix, x), - sacral outflow. Parasympathetic ganglia usually lie close to or within the target organ. Sympathetic outflow leaves the CNS in thoracic and lumbar spinal root sympathetic ganglia form two paravertebral chains, plus some midline ganglia. The enteric nervous system consists of neurons lying in the intramural plexuses of the gastrointestinal tract. It receives inputs from sympathetic and parasympathetic systems but can act on its own to control the motor and secretory functions of the intestine.

10. Transmitters In The Autonomic Nervous System The two main neurotransmitters that operate in the autonomic system are Acetylcholine and Noradrenalin. All motor nerve fibers leaving the CNS release acetylcholine, which acts on nicotinic receptors All postganglionic parasympathetic fibers release acetylcholine, which acts on muscarinic receptors All postganglionic sympathetic fibers ( with one important exception) release noradrenalin, which may act on either α- or β- adrenoceptors.

11. The exception is the sympathetic innervation of sweat glands, where transmission is caused by acetylcholine acting on muscarinic receptors. Presynaptic Modulation Presynaptic receptors regulate transmitter release mainly by affecting Ca2+ entry into the nerve terminal. Most presynaptic receptors are of the G- protein-couple type, which control the function of calcium and potassium channels, either through second messengers that regulates the state of phosphorylation of channel protein or by a direct interaction of G-protein with the channels.

12. Transmitter release is inhibited when calcium channel opening is inhibited, or when potassium channel opening is increased, in many cases, both mechanisms operate simultaneously. Presynaptic regulation by receptors linked directly to ion channel (ionotropic receptors), rather than to G-proteins also occurs. Nicotinic acetylcholine receptors are particularly important in this respect. They facilitate the release of other transmitters, such as glutamate, and it is believed that most of the nicotine receptors expressed in the CNS are located presynaptically.

14. Postsynaptic Modulation Chemical mediators often act on postsynaptic structures, including neurons, smooth muscle cells, cardiac muscle cells etc, in such a way that their excitability or spontaneous firing pattern is altered. In many case, as with presynaptic modulation, the mechanisms appear to involve changes in calcium and /or potassium channels functions mediated by a second messenger. The slow excitatory effect produced by various mediators, including acetylcholine and peptides such as substance P on many peripheral and central neurons results mainly from decrease in K+ permeability.

15. By comparison the inhibitory effect of various opiates mainly a result of increased K+ permeability. Transmitter Other than Acetylcholine And Noradrenaline Non – noradrenergic non-cholinergic (NANC) ATP, vasoactive intestinal peptides, neuropeptides, Y and nitric oxide, substance P, 5-HT,GABA and dopamine (which play a role in ganglionic transmission. Termination of Transmitter Action

16. Basic Steps In Neurochemical Transmission : Sites of Drug Actions