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32 Cards in this Set
- Front
- Back
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Criteria for accepting a substance as a transmitter (4)
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1) It must be synthesized in the neuron with the enzymes needed for its synthesis being present in the neuron
*exceptions are gases 2) it must be released in sufficient quantity to elicit a response from the postsynaptic target 3) mechanisms for its removal or inactivation from the synaptic cleft must exist 4) it should mimic the action of the endogenously released NT when administered exogenously at or near a synapse |
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Main features of the NT Life Cycle (6)
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1. Synthesis
2. Packaging & storage into synaptic vesicles 3. Transport to the active zone 4. Following an AP and an influx of [Ca2+]i, fusion with the plasma membrane 5. Binding of the NT to its receptor on the post-synaptic cell 6. Termination of its action by diffusion, destruction or re-uptake into cells |
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Main agonists and antagonists for nAChR, mAChR, α-adrenergicR and β-adrenergicR
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• Agonists
- nAChR = Nicotine - mAChR = Muscarine - α-adrenergicR = Phenylephrine - β-adrenergicR = Isoproterenol • Antagonists - nAChR = D-tubocurarine - mAChR = Atropine - α-adrenergicR = Phenoxybenzamine - β-adrenergicR = Propranolol |
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Differences btwn nAChR and mAChR (3)
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nAChR are ionotropic receptors that facilitate the opening of v-gated Na+ channels while
mAChR are metabotropic receptors that use a G-protein to activate a signaling cascade inside the cell Though both receptors have ACh as an NT, they have different agonists and antagonists: • Agonists - nAChR = Nicotine - mAChR = Muscarine • Antagonists - nAChR = D-tubocurarine - mAChR = Atropine |
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The mechanisms of action of ACh on:
• Exocrine gland cells • Smooth muscle cells • Cardiac Pacemaker cells |
The mechanisms of action of ACh on:
• Both Exocrine gland cells and Smooth muscle cells use the following PL-C pathway - ACh binds to M3-muscarinic receptors in the secretory cells of glands - The receptor activates a G-protein which activates PL-C - PL-C activity produces two 2nd messengers, DAG and IP3, leading to a rise in [Ca2+]i - secretion of stored enzymes is enhanced, leading to increased ion and water transport • Cardiac Pacemaker cells - ACh binds to an M2-Muscarinic receptor which activates an inhibitory G-protein, Gqi - Gqi reduces the activity of adenylyl cyclase, leading to a fall in [cAMP] - This leads to indirect closure of Ca2+ channels and a weaker spontaneous depolarization of cells |
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Mechanism of action of NorAdrenaline on Cardiac cells and pacemaker cells
- How does this ultimately affect the conductance of certain ions? |
• Cardiac muscle fibers have β-1-adrenergic receptors
• NorA binds to the receptors and activates a G-protein which increases adenylyl cyclase activity • adenylyl cyclase increases [cAMP]i which leads to Phophorylation of membrane channels causes the following: - g(K+) falls, increasing the rate of spontaneous depolarization - g(Ca2+) rises causes ventricular cells to yield stronger contractions , increasing cardiac output |
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The cellular distribution of ACh and Catecholamine receptors
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ACh receptors are typically found on the end plate of muscle fibers as well as on smooth muscle, Sympathetic & Parasympathetic ganglia and in the CNS
Catecholamine receptors are found in smooth muscle, cardiac muscle and glands |
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Neuropeptides:
• duration of effects when compared to other NTs • How they are inactivated |
Neuropeptides:
• relatively long lasting • Inactivated through diffusion and breakdown by cellular processes |
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Gaseous NTs bind to this enzyme and stimulate the production of this 2nd messenger
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Enzyme - Guanayly cyclase
2nd messenger - GTP |
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Two enzymes that can be used to break down catecholamines and monoamines
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MOA and COMT
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Muscarinic AChR:
• The 5 types of receptors • The major muscarinic brain receptors • The excitatory receptors > the G-protein and enzyme they activate • The inhibitory receptors > The G-protein they activate and enzyme they inhibit > The ion channels they regulate • The significance of the M2 AChR |
Muscarinic AChR:
• M1 - M5 • M1, 3 and 4 > Gs, PLC • M2 & 4 > Gi, adenylate cyclase > K+ and Ca2+ • It is a heart isoform, expressed sparingly in other organs |
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Gastric Acid secretion involved this mAChR
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M1
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Eccrine and Sweat glands:
• Two examples • The NT and receptor involved in their stimulation |
Eccrine and Sweat glands:
• eccrine sweat glands and lacrimal glands • ACh, M3 receptors |
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Pacemaker cells of the Heart:
• The neurons that iNN them • Have this mAChR type • Actions of the receptor - activates this protein which affects this enzyme - the physiological result (2) |
Pacemaker cells of the Heart:
• Post-ganglionic parasympathetic • M2 • Actions of the receptor - activates a Gprotein, Gi, which reduces the activity of adenylate cyclase - Heart rate/Cardiac output decreases - Weaker depolarization of cells due to Ca2+ channel closure caused by decreased [cAMP] |
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The Shortcut pathway involving Cardiac Pacemaker cells:
• The overall goal of the pathway • Involves this protein • These ion channels open leading to this event • The affects of conductance on two ions |
The Shortcut pathway involving Cardiac Pacemaker cells:
• The goal is to slow down heartrate • G protein, Gqi subunit • K+, leading to hyperpolarization • g(K+) increases g(Ca2+) decreases |
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Mechanism of action by glycine:
• Type of NT • Most common area used in the body • Types of receptors it binds • Its receptor needs this many Gly molecules to bind |
Mechanism of action by glycine:
• is an inhibitory NT • Most commonly used in the spinal cord • Binds to an ionotropic receptor in that area • Its receptor needs 3 Gly molecules to bind |
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Mechanism of action by GABA:
• Type of NT • mainly fxns in these areas • its receptors need this many GABA to bind • can bind these two different types of receptors • the fxn of these receptors |
Mechanism of action by GABA:
• is an inhibitory NT • mainly fxns in the brain and brain stem • two • GABA(a) - is a ionotropic receptor that mediate fast IPSPs and and GABA(b) - is a metabotropic receptor which indirectly causes K+ channels to open through 2nd messengers. Ultimately, they mediate slow IPSPs of the post-synaptic neuron |
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The ascending arousal system:
• Two transmitters that participate • The primary locations of their neurons • When the above neurons have suboptimal activity, this results |
The ascending arousal system:
• Noradrenaline and Serotonin • Noradrenergic neurons - located in the pons, locus ceruleus Seronergic neurons located in the brain stem, rostral raphe • Suboptimal activity of these neurons lead to feelings of anxiety, despair and fear. |
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Adrenergic Receptors:
• are classified as these type of receptors • their agonists • their two groups • How the subtypes of their groups are classified |
Adrenergic Receptors:
• Metabotropic, G-protein • Catecholamines • α and β • the subtypes of the above are classified by their different orders of potency for agonists and different antagonists |
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Clinical depression:
• due to this impairment • two possible tx |
Clinical depression:
• due to impaired serotonergic transmission in the CNS • SSRIs or MAO inhibitors |
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Describe the 4 synthesis rxns of Adreneline:
What type of cells are involved? Where are certain enzymes located? |
• Catecholinergic neurons synthesize dopamine, adreneline and Noradreneline
• The rxns: 1. Tyr ---> L-Dopa (Tyr Hydroxylase) 2. L-Dopa ---> Dopamine (DOPA Decarboxylase) 3. Dopamine ---> Noradrenaline (DBH) * DBH is only found in the membrane of synaptic vesicles of catecholaminergic neurons and the adrenal medulla 4. Noradrenaline ---> Adrenaline (PEA-N-MT) |
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Nocioreceptors:
• Originate here and project to this area • release this NT (2 names) • What this NT transmits • Consequence of prolonged interaction with capsaicin |
Nocioreceptors:
• Originate in the DRG and project to the spinal cord • Substance P or tachykinin • It transmits info about pain, mainly increased pain sensation • It causes death to the primary afferent neurons, leading to decrease of Substance P release |
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Cardiac Muscle:
• The types of nerves that stimulate them • The type of receptors it has • The conductance of these ions are affected • The physiological result (2) |
Cardiac Muscle:
• Post-ganglionic sympathetic • β1-adrenergic • g(K+) decreases g(Ca2+) increases • Stronger contraction, larger cardiac output |
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Metabotropic Dopamine receptors:
• Affect the activity of this enzyme • Number of types • Is categorized into two groups - its members - what it does • The receptor that's targeted for tx in Parkinson's |
Metabotropic Dopamine receptors:
• Affect adenylate cyclase activity • Five • D1-like - D1 and D5 - fxns to increase cAMP production D2-like - D (2, 3 & 4) - Inhibit production of cAMP • D2 receptor |
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Glutamate:
• is an example of a NT with these receptor types • the two different forms of ionotropic receptors it has are AMPA and Kainate - AMPA > the ions it mediates and in which direction - AMPA > The ions it mediates and in which directions > The ion that can block it > The channels is thought to be involved in this cognitive fxn • Metabotropic Glu receptors can be found on these cells |
Glutamate:
• can bind to both ionotropic and metabotropic receptors • the two different forms of ionotropic receptors it has are AMPA and Kainate - AMPA > Na+ K+ out of the cell - AMPA > Na+ and Ca2+ into the the cell K+ out of the cell > Mg2+ > Memory processing • Bipolar ells of the retina |
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Opioid peptides:
• the 3 endogenous families • The common 5 AA sequence for all families (2 versions) • They mimics the action of thi molecule |
Opioid peptides:
• β-endorphins, enkephalins and dynorphins • Tyr-Gly-Gly-Phe-Leu or Tyr-Gly-Gly-Phe-Met • They mimics the action of morphine |
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Problem with using opiod peptides as pain tx
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They do not cross the BBB so there is not an effective means of delivering them into the CNS
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Pilocarpine:
• is an agonist for this NT and receptor • affects this part of the nervous system • Clinical tx |
Pilocarpine:
• is an agonist for ACh and the mAChR • affects the PNS • Used to treat glaucoma since it can reduce intraocular pressure in the eye |
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Beta Blockers:
• an antagonist of these receptors • what they antagonize • Clinical tx • an example |
β-Blockers:
• an antagonist of β-1 receptors • They antagonize the action of vasoconstriction produced by NorA along with its action on heart rate • Clinical tx for hypertension • Propranolol |
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Agonists of Beta-2 receptors:
• their mode of action + clinical tx • example |
Agonists of β-2 receptors:
• used to relax smooth muscle in the bronchioles during an asthma attack • Salbutamol |
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Agonists of α-1 receptors
• Their mode of action • example |
Agonists of α-1 receptors
• Used to cause vasoconstriction in the nasal cavity to reduce congestion • Phenylephrine |
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Horner's Syndrome:
• Etiology • result • symptoms (4) |
Horner's Syndrome:
• Unilateral lesion in the CNS pathway • paralysis of the radial smooth muscle of the iris • miosis, partial ptosis, anhydrosis and enophthalmos |
