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Chaps 4 & 5: Receptors As Drug Targets, Structure, Function & Signal Transduction

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Chaps 4 & 5: Receptors As Drug Targets, Structure, Function & Signal Transduction Chaps 4 & 5: Receptors as drug targets, structure, function & signal transduction Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. Communication allows cells to perceive and correctly respond to their microenvironment for proper development, tissue repair, and immunity and normal tissue function. Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity, diabetes and more. Understanding cell signaling is crucial for treating diseases effectively. signals neighbor receptors (neurotransmitters) self talk talk cell 1 signals cell 2 cell 1 cell 2 cell 3 etc. synapse synapse synapse signals signals receptor a (hormones) (hormones) receptor b cell 2 cell 3 The same signal can deliver different cell 1 messages to different tissues (histamine). cell 5 cell 4 receptor c signals signals (hormones) (hormones) receptor d Important functions of receptors: 1. Globular proteins (receptors) acting as a cell’s ‘letter boxes’ 2. Located mostly in the cell membrane 3. Receive messages from chemical messengers coming from other cells 4. Transmit a message into the cell leading to a cellular effect 5. Different receptors specific for different chemical messengers 6. Each cell has a range of receptors in the cell membrane making it responsive to different chemical messengers 1 © Oxford University Press, 2013 Signals can be divided into the 5 catagories below. Signal carriers (S) have to reach the proper receptors (R) for the message to be recieved. Intracrine signals are produced by the target cell that stay within the target cell. cell a S = signal S R R = receptor Autocrine signals are produced by the target cell, are secreted, and affect the target cell itself via receptors. Sometimes autocrine cellscantarget cellsclose by if they arethe same type of cell as the emitting cell. An example of this are immune cells. cell a S R Juxtacrine signals target adjacent (touching) cells. These signals are transmitted along cell membranes via protein or lipid components integral to the membrane and are capable of affecting either the emitting cell or cells immediately adjacent. R S cell a R cell b Paracrine signals target cells in the vicinity of the emitting cell. Neurotransmitters represent an example. S R cell a cell b S R cell c S etc. synapse synapse synapse Endocrine signals target distant cells. Endocrine cells produce hormones that travel through the blood to reach all parts of the body (long-range allostery). S S R2 cell c S S S S cell a S S S S S S S R3 cell d R1 cell b 2 © Oxford University Press, 2013 Central Nervous System (CNS) structure Brain and spinal cord Integrative and control centers, function process info out and info in Peripheral Nervous System (PNS) Cranial nerves and spinal nerves Communication lines between the CNS and the rest of the body Sensory (afferent) division Motor (efferent) division (CNS) Somatic and visceral sensory Motor nerve fibers nerve fibers Conducts impulses from Conducts impulses from the CNS receptors to the CNS to effectors (muscles and glands) Sympathatic division Autonomic nervous system (ANS) Somatic nervous system mobilizes body systems during activity (fight or flight) Visceral motor (involuntary) Somatic motor (voluntary) Conducts impulses from the CNS to Conducts impulses from the cardiac muscles, smooth muscles, CNS to skeletal muscles Parasympathetic division and glands Conserves energy Promotes 'housekeeping' functions during rest 3 © Oxford University Press, 2013 Central nervous system The central nervous system consists of the two major structures: the brain and spinal cord. The brain is encased in the skllkull, an d pro tect tdbthed by the crani um. The spinal cord is continuous with the brain and lies on the backside to the bibrain, an did is pro ttdbthtected by the vert tbebra. The spinal cord reaches from the base of the skull, continues through or starting below the foramen magnum, and term inat es roughl y l evel with th e fi rst or second lumbar vertebra, occupying the upper sections of the vertebral canal. The CNS in tegra tes in forma tion it receives from, and coordinates and influences the activity of, all parts of the body and it contains the majority of the nervous system. Usua lly, the reti na and the optic nerve (2nd cranial nerve), as well as the olfactory nerves (1st) and olfactory epithelium are considered as parts of the CNS, s ynapsing directly on brain tissue without intermediate ganglia.. 4 © Oxford University Press, 2013 Peripheral nervous system The peripheral nervous system (PNS) is the part of the nervous system that consists of the nerves and ganglia on the outside of the brain and spinal cord . Its main function is to connect the central nervous system (CNS) to the limbs and organs, essentially serving as a communication relay going back and forth between the brain and spinal cord with the rest of the body. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain barrier, which leaves it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system 5 © Oxford University Press, 2013 The autonomic nervous system is responsible for regulating the body's unconscious actions. The parasympathetic system is responsible for stimulation of "rest-and-digest" or "feed and breed" activities that occur when the body is at rest, especially after eating, including sexual arousal, salivation,,(),,g lacrimation (tears), urination, digestion and defecation. Its action is described as bein g complementary to that of the sympathetic nervous system, which is responsible for stimulating activities associated with the fight-or-flight response. Parasympathetic nervous system Sympathetic nervous system 6 © Oxford University Press, 2013 The somatic nervous system is the part of the peripheral nervous system associated with skeletal muscle voluntary control of body movements. It consists of afferent nerves Somatic nervous system (toward) and efferent nerves (out of). Afferent nerves are responsible for relaying sensation from the body to the central nervous system (CNS); efferent nerves are responsible for sending out commands from the CNS to the body. There are 43 segments of nerves in the human body. With each segment, there is a pair of sensory and motor nerves. In the body, 31 segments of nerves are in the spinal cord and 12 are in the brain stem . The somatic nervous system consists of three parts: Spinal nerves: They are peripheral nerves that carry sensory ifinformat ion into and motor command s out of fh the spinal cord. Cranial nerves: They are the nerve fibers that carry information into and out of the brain stem. They include smell, vision, eye, eye muscles, mouth, taste, ear, neck, shoulders, and tongue. Interneurons (association nerves): These nerves integrate sensory input and motor output , numbering thousands 7 © Oxford University Press, 2013 Nerve cells make contact to muscle cells, organs and other nerve cells Can be 1000s of axon inputs from other nerve cells. … or synaptic button when contact to neuron 8 © Oxford University Press, 2013 axon Synaptic button or neuromuscular junction Cell body 9 © Oxford University Press, 2013 Nerve cells and glial cells are incredibly complicated networks of connections. Perhaps, 100,000,000,000 neurons with 10,000 connections each 1,000,000,000,000,000 (quadrillion). 10 © Oxford University Press, 2013 Neurological disorders Charcot–Marie–Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN), here ditary sensor imo tor neuropa thy and peroneal muscul ar at roph y, i s a h et erogeneous inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease. Presently incurable, this disease is one of the most common inherited neurolog ical di sord ers, with 37 in 100, 000 aff ec ted ( 1 in 2500). Alzheimer's disease (AD), is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or bhbehav iora l c hanges. ThdiThe disease process is assoc itdiated with ithl plaques and dt tangl es i n th thbe brai n. Th e most striking early symptom is loss of short-term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment exten ds to th e d omai ns of l anguage, skill ed movement s and recogniti on, and f uncti ons such as decision-making and planning become impaired. Parkinson's disease (PD), is a degenerative disorder of the central nervous system that often impa irs the suff erer' s mot or skill s an d speec h. PkiParkinson 'di's disease blbelongs t o a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement, and in extreme cases, a loss of physical movement). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused btheby the insufficient formation and action of dopamine , which is prod u ced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive. 11 © Oxford University Press, 2013 Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatigability during simple activities. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Demyelination results in the loss of the myelin sheath insulating the nerves.
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