YR1 Lecture 1H - Communication Systems - Dr David Mahns 2022.pdf

Communication systems Associate Professor David Mahns Associate Dean Research School of Medicine Western Sydney University E: [email protected] 1 Learning Objectives Compare and contrast the differences between hormone and nervous system communication around the body References Textbook o...

Communication systems Associate Professor David Mahns Associate Dean Research School of Medicine Western Sydney University E: [email protected] 1 Learning Objectives Compare and contrast the differences between hormone and nervous system communication around the body References Textbook of Medical Physiology Guyton & Hall, 10th edition, 2000, Saunders Medical Physiology Boron & Boulpaep, 2005, Elsevier Saunders 2 Compare and contrast the differences between hormone and nervous system communication around the body Nerves Rapid onset of action Often brief effects Often very localised effects Eg Hormones Slower onset of action Often maintained effects Often very general effects - Voluntary contraction of skeletal muscle - Autonomic control heart rate / BP 3 Contraction of skeletal muscle Muscle composed of multiple muscle fibres Innervated by motor nerve fibres (alpha motor neuron) Individual nerve fibres innervates multiple muscle fibres. Individual muscles fibres are innervated by one nerve Motor Unit: Group of muscle fibres controlled by a single motor nerve 4 Neuromuscular junction Innervated by motor nerve fibres (alpha motor neuron) acetylcholine nicotinic receptors   Na+ Conductance  depolarisation (more +ve) muscle action potential  depolarisation (more +ve)   [Ca2+] muscle contraction 5 Neuromuscular junction Innervated by motor nerve fibres (alpha motor neuron) acetylcholine nicotinic receptors   Na+ Conductance  depolarisation (more +ve) muscle action potential  depolarisation (more +ve)   [Ca2+] muscle contraction 6 Innervated by motor nerve fibres eg Autonomic nervous system Acetylcholine (X –Parasympathetic) Muscarinic receptors  Activate second messenger (g proteins)  Activate K+ channels  hyper depolarisation (more -ve) Decrease in heart rate 7 Magnitude of effect regulated by: 1. 2. 3. 4. period of availability in synapse post-synaptic receptor availability post-synaptic receptor excitability/ responsiveness amount of transmitter released 8 1. Period of availability in synapse washout, diffusion, metabolism e.g., AChE for Ach post-synaptic uptake e.g., corticosterone for NA pre-synaptic uptake Increased / decreased intraneuronal metabolism e.g., cocaine, desipramine, tricyclic anti-depressants (NA uptake) 9 2. Post-synaptic receptor availability receptor antagonists e.g., α, β-blockers pathological conditions e.g., reduced ACh receptor numbers drugs that up or downregulate receptor number e.g., nicotine (down) 10 3. Post-synaptic excitability/ responsiveness inhibitory neurotransmitters e.g., GABA drugs e.g., channel blockers hormones e.g., angiotensin II local tissue factors, metabolites e.g., NO, ATP, H+, K+ 11 4. Amount of transmitter released number of impulses per unit time chemical environment in vicinity of nerve terminal note: amount of available calcium is not likely to be a limiting factor; [Ca2+] very closely regulated 12 4. Amount of transmitter released Effects of chemical environment in vicinity of nerve terminal i. neurotransmitter released from that nerve - Auto-regulation ii. co-transmitters released from the nerve iii. neurotransmitters / co-transmitters from adjacent terminals - Cross-talk iv. Local tissue factors / Physio-chemical environment v. Hormones vi. Neuroactive, psychoactive drugs 13 (i) neurotransmitter released from that nerve Autoregulation 14 e.g., Noradrenaline on nerve terminal (presynaptic α2adrenoceptors NA NA 15 (ii) co-transmitters released from the nerve NPY (Neuropeptide Y) and ATP released with Noradrenaline VIP released with Acetylcholine opioid peptides etc. etc. 16 Sympathetic Nervous System (varicosity) Short acting Seconds-minutes Long acting minutes-hours 17 (iii) neurotransmitters / co-transmitters from adjacent terminals interplay between noradrenergic and cholinergic neurons in the heart an blood vessels. interplay between dopaminergic, glutamatergic and cholinergic nerves in CNS 18 (iv) local tissue factors / Physiochemical environment produced as a result of normal metabolism e.g. adenosine, NO, H+ produced as a consequence of trauma etc. e.g. histamine, serotonin, bradykinin pH, high Na+/ Low K+, altered osmolarity (v) hormones Angiotensin II (salt / H20) Adrenaline (stress / fear) Opioids (stress / pain) etc. etc. (vi) Neuroactive / psychoactive drugs Therapeutic (MAO inhibitor/ reuptake inhibitors) socially abused note: synapse very vulnerable to chemical environment19 20 Observe now, you have 2 years to explore interactions and their relevance. 21 Hormones Chemical signalers and regulators Liberated from one site Transported by the blood Have effects at a distant site 22 Where are the hormone secreting cells? Clusters of specialised cells in discrete ‘endocrine glands’ e.g., thyroid gland, adrenal glands Clusters of specialised cells embedded within other organs and tissues e.g., gastrin secreting cells in stomach, erythropoietin secreting cells in kidney 23 Pineal gland Pituitary gland Thyroid gland Parathyroid glands (behind thyroid) (Thymus) Adrenal glands Endocrine pancreas Ovaries (Testes) 24 Key concepts 1 and 1a Hormones are chemical compounds that communicate regulating signals to distant cells Neurotransmitters are chemical compounds that communicate regulating signals to adjacent cells 25 Key concept 2 Hormones are chemically diverse Derived from a single amino acid e.g., adrenaline, melatonin, thyroxin Some are polypeptides e.g., angiotensin II, growth hormone etc Some are steroid compounds, derived from cholesterol e.g., cortisol, testosterone, aldosterone etc 26 Key concept 3 Hormones are released by diverse stimuli Chemical environment e.g., glucagon and insulin in response to blood glucose levels Neural e.g., adrenaline, oxytocin Other hormones (‘releasing hormones’, trophic hormones e.g., growth hormone releasing hormone (GHRH); adrenocorticotrophic hormone (ACTH) 27 Transport of Hormones Water soluble hormones – in solution in plasma e.g. adrenaline, calcitonin Non-water soluble hormones – bound to plasma proteins e.g., thyroxin, cortisol Bound Hormone inactive (90 – 99.9%) Free Hormone (0.1 – 10%) biologically active 28 Key concept 4 Hormones exert action by binding to receptors on or in target cells ∆ ion permeability of the membrane  activate or inhibit cell activity stimulate production of intracellular compounds (second messengers)  trigger or regulate cellular activity e.g., glucagon, parathyroid hormone entering the target cell and altering gene expression to change the amount of key enzymes or other proteins produced e.g., cortisol, aldosterone (steroid) 29 Key concept 5 Hormones exert action over variable time spans Some hormones have ½ lives of seconds/minutes e.g., adrenaline, angiotensin II Some have ½ -lives of minutes/hours e.g., insulin, cortisol Some of hours/days e.g., growth hormone, thyroxin Neurotransmitters Milliseconds to seconds 30 Key concept 6 Hormone release is regulated By levels of the substance it is regulating (feed back) e.g., glucose, plasma Ca2+, stomach pH By levels of itself in the plasma e.g., thyroxin, ACTH By a Hierarchical / Neuroendocrine Systems e.g., adrenaline, antidiuretic hormone [ADH] 31 Key concept 6 Hormone release is regulated By levels of the substance it is regulating (feed back) e.g., glucose, plasma Ca2+, stomach pH By levels of itself in the plasma e.g., thyroxin, ACTH By a Hierarchical / Neuroendocrine Systems e.g., adrenaline, antidiuretic hormone [ADH] 32 -ve Feedback e.g., thyroid function +ve Feedback Parturition Thyrotropin releasing hormone Thyrotropin (Thyroid Stimulating Hormone) Thyroid gland Thyroxin, tri-iodo-thyronine (T4, T3) Self – limiting 33 Self perpetuating / enhances activity Signalling and regulation Slower Onset versus Faster Onset e.g., hormones vs neurons Brief Response versus Maintained Response e.g., neurones vs hormones Specific versus Intermediate versus General e.g., neurones vs hormones Local versus Distant e.g., autocrine, paracrine vs endocrine and neuronal 34 References Textbook of Medical Physiology Guyton & Hall, 10th edition, 2000, Saunders Medical Physiology Boron & Boulpaep, 2005, Elsevier Saunders Human Physiology Rhoades & Pflanzer, 4th edition, 2003, Thomson 35