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Learning Objectives Define neurotransmitters Enlist the neurotransmitter of locomotor system. Give their structure. Enlist different neurotransmitter receptors Give the synthesis of these neurotransmitters. Justify that acetylcholine has sympathetic & parasympathetic functions. Explain the mechanism of action of acetylcholine in modulating muscle contraction. Give the receptors through which these neurotransmitters carry out these functions. Lecture outline Definition Neurotransmitters are substances that are produced by neurons, stored in the synapses, and released into the synaptic cleft in response to a stimulus. Important neurotransmitters Neurotransmitters can be classified into several groups according to their chemical structure. Types of Receptors Like all signaling substances, neurotransmitters act via receptor proteins. The receptors for neurotransmitters are integrated into the membrane of the postsynaptic cell, where they trigger ion inflow or signal transduction processes The receptors for neurotransmitters are divided into two large groups according to the effect produced by binding of the transmitter Two large groups according to their mode of action. 1 Ionotropic receptors 2 Metabotropic receptors Ionotropic receptors They are ligand-gated ion channels. The receptors for stimulatory transmitters mediate the inflow of cations (mainly Na+). When these open after binding of the transmitter, local depolarization of the postsynaptic membrane occurs. By contrast, inhibitory neurotransmitters (GABA and glycine) allow Cl– to flow in. This increases the membrane’s negative resting potential and hinders the action of stimulatory transmitters (hyperpolarization) Metabotropic receptors They are coupled to G proteins, through which they influence the synthesis of second messengers. Receptors that work with type Gs proteins increase the cAMP level in the postsynaptic cell (cAMP), while those that activate Gi proteins reduce it. Via type Gq proteins,other receptors increase the intracellular Ca2+ concentration. Neurotransmitters of Locomotor System Acetylcholine (ACh) was the neurotransmitter first discovered, at the beginning of the last century. It binds to two types of receptor. The nicotinic ACh receptor responds to the alkaloid nicotine contained in tobacco this). The nicotinic receptor is ionotropic The muscarinic ACh receptors are metabotropic Acetylcholine, the acetic acid ester of the cationic alcohol choline acts at neuromuscular junctions, where it triggers muscle contraction and in certain parts of the brain and in the autonomous nervous system. The muscarinic ACh receptors influence the cAMP level in the postsynaptic cells Acetylcholine receptors Synthesis Acetylcholine is synthesized from acetyl-CoA and choline in the cytoplasm of the presynaptic axon and is stored in synaptic vesicles, each of which contains around 1000–10 000 ACh molecules. After it is released by exocytosis, the transmitter travels by diffusion to the receptors on the postsynaptic membrane. Catalyzed by acetylcholinesterase, hydrolysis of ACh to acetate and choline immediately starts in the synaptic cleft and within a few milliseconds, the ACh released has been eliminated again. The cleavage products choline and acetate are taken up again by the presynaptic neuron and reused for acetylcholine synthesis.