Biochemistry - Nervous System

Functional distinctions in the nervous system 1. Central / peripheral nervous system: • Central: Brain and spinal cord • Peripheral: Nerves connecting the CNS with the rest of the body; ganglia (nodes) halfway between CNS and target organs, and plexus (braids) in the internal organs 2. Somatic / autonomic nervous system: • Somatic: Concerned with conscious, voluntary activity and perception (Skeletal muscle, sensory receptors and nerves). • Autonomic: Involuntary control of internal organs. Examples: Blood pressure, heart rate, sweat glands Schematic of a nerve cell Dendrites Terminal buttons Synapse Soma Axon Soma = body (greek) Synapse = junction Dendron = tree button = button (engl.) Neurons are controlled by excitatory and inhibitory afferent synapses Different anatomical types of synapses neuro-neural neuromuscular (skeletal muscle; ‘myoneural junction’) neuromuscular (smooth muscle) Muscle fibers and a branching nerve ending EM of a synapse How a synapse works Transmitter Action potential Ca + + Voltage-sensitive channel Receptor Ca++ in neurotransmitter exocytosis Action potential + Synapsin CaM Kinase II P Ca++ Synaptotagmin Synaptobrevin Ca++ Synaptic transmission is an important target of drug action (1) Agonists (‘mimetic’ drugs) can augment or entirely substitute the effect of a neurotransmitter + + + Synaptic transmission is an important target of drug action (2) Antagonists (‘lytic’ drugs) can inhibit or entirely abrogate the effect of a neurotransmitter - Synaptic transmission is an important target of drug action (3) ‘Indirect mimetic’ drugs can promote the effect of the transmitter by interfering with its inactivation reuptake enzymatic inactivation Synaptic transmission is an important target of drug action (4) Presynaptic receptors form a feedback loop that can be selectively targeted by agonists and antagonists Indirect agonists and antagonists may modify the availability of transmitter storage synthesis breakdown reuptake enzymatic inactivation Types of synapses: Transmitters Some important transmitter substances are: CH3 H3C C O O C H2 C H2 N + Acetylcholine CH3 CH3 H2 C HC OH H2N HC CH CH Norepinephrine (Noradrenaline) HO OH More transmitters COOH H2N CH CH2 CH2 COOH COOH CH2 Glutamate Glycine NH2 H2N H2 C CH2 CH2 COOH -Aminobutyrate (GABA) Tyr-Gly-Gly-Phe-Met-ThrSer-Glu-Lys-Ser-Gln-ThrPro-Leu-Too-Muc-Hse-XmaKes-You-Sho-Rts-Igh-TedVal-Lys-Asn-Ala-His-LysLys-Gly-Gln -Endorphin …and many more… Neurotransmitter receptors • Ligand – gated channels: • Nicotinic acetylcholine receptor • NMDA-type glutamate receptor • Glycine receptor • GABAA receptor • Serotonin receptor (5-HT3,) • G protein-coupled receptors: • Muscarinic acetylcholine receptor (several types) • ‘Metabolic’ glutamate receptors • Catecholamine receptors • 5-HT receptors other than 5-HT3 • GABAB receptors • Peptide receptors Medulla oblongata Ganglia N M Heart Smooth muscle ,  in gut and blood vessels Glands M N M D1 N Spinal cord N Kidney arteries Adrenal gland Skeletal muscle N Parasympathetic Sympathetic Somatic Synapses in the autonomic nervous system as drug targets Why target the autonomic nervous system? It controls Heart rate Blood pressure Blood flow distribution Motility of the digestive tract Bronchial contraction / dilatation and secretion 6. Body temperature; sweating 1. 2. 3. 4. 5. Hypertension, cardiovascular disease Surgical patients Surgical patients Asthma / bronchitis ‘Mydriasis’ = wide pupils Sympathetic stimulation Parasympathetic stimulation ‘Miosis’ = narrow pupils ‘Mydriasis’ = wide pupils Sympathetic stimulation (cocaine, ‘speed’) Parasympathetic stimulation -opiod receptors (heroin) ‘pinpoint pupils’ The nervous and the endocrine system are not cleanly separated Somatic NS Autonomic NS Endocrine system Acetylcholine Noradrenaline Somatic NS Autonomic NS Endocrine system Different anatomical types of synapses neuro-neural neuromuscular (skeletal muscle; ‘myoneural junction’) neuromuscular (smooth muscle) Portal vessels may direct hormones to specific tissues CRH, … Neurons in the hypothalamus anterior lobe: ACTH, … Hypophyseal gland posterior lobe: oxytocin, vasopressin