Neurotransmission II Flashcards
What are some examples of GPCR coupled to Gs that activate adenylate cyclase and increase cAMP?
Beta-adrenergic, dopamine-1, 5-HT-5/7
What are some examples of monoamines?
Epinephrine, norepinephrine, serotonin, dopamine, histamine
What are some examples of GPCR’s coupled to Gi that deactivates adenylate cyclase and decreases cAMP?
Alpha-2-adrenergic, muscarinic-2, dopamine-2, and 5HT-1
What are some examples of GPCR’s coupled to Gq that activate phospholipase C and increase levels of DAG and IP3 and Ca2+?
Alpha-1-adrenergic, muscarinic-3, 5-HT-2
What is a mechanism that decreases the response of the GPCR’s to neurotransmitters or other ligands (agonists) when these are in high concentration, process involves phosphorylation of the receptor followed by uncoupling from the G protein but the number of receptors in the plasma membrane does not change?
Receptor desensitization
What is a process that involves sequestration of the receptor from the plasma membrane via internalization and in some case degradation of the receptor thereby decreases the number of receptors in the cell surface?
Receptor down regulation
What are considered major mechanisms underlying tolerance to certain drugs of abuse and prescription drugs?
Receptor desensitization and down regulation
What type of neurons are localized in the substantia nigra pars compacta, ventral tegmental area (VTA) and the tuberohypophysial ( from hypothalamus to pituitary) pathways?
Dopaminergic (DA) neurons
What type of neurons are located in the locus ceruleus and loose clusters of neurons in the brain stem?
Noradrenergic (NE) neurons
What type of neurons are located in the raphe nuclei, a moderate size cluster of nuclei found in the brainstem?
Serotonergic (5-HT) neurons
What is the main substrate in dopamine synthesis?
Tyrosine (Tyr)
Tyr is transported across the BBB via what?
Large neutral amino acid transporter (LNAAT)
LNAAT transports all LNAA (Tyr, Phe, Trp) and what other similar compound?
L-Dopa
Tyr is compromised in patients with what disorder?
PKU
What is a monooxygenase that requires BH4 as a cofactor, the rate limiting enzyme in monoamine biosynthesis and converts Tyr to L-Dopa?
Tyrosine hydroxylase (TH)
What substrate of the Tyr synthesis reaction is used to treat patients with Parkinson’s disease?
L-Dopa
What is a non specific decarboxylase that catalyzes the RXN of L-Dopa to dopamine?
Aromatic amino acid decarboxylase (AAAD)
What 2 enzymes can be used in the degradation of dopamine?
COMT and MAO
What is present in the extracellular compartment and inhibition of it is used as a treatment for Parkinson’s disease?
COMT
What type of MAO is selective for dopamine and it’s inhibitor is used in the treatment of Parkinson’s disease?
MAO-B
What type of MAO is used for NE and 5HT and along with the other type it’s inhibitor can be used to treat depression?
MAO-A
What is a MA/proton antiporter that concentrates MA in synaptic vessels?
VMAT2
What type of transporters are targets for prescription drugs and drugs of abuse that mediate the re uptake of the specific monoamine from the synaptic cleft?
Specific transporters for each of the amines (dopamine transporter - DAT, norepinephrine - NET, serotonin - SERT)
What enzyme further hydroxylizes dopamine to NE?
Dopamine beta hydroxylase (DBH)
What 2 enzymes are involved in the synthesis of NE to Epi?
Phenylethanolamine and N-methyl transferase
Sense serotonin is not a catecholamine it can only be degraded by what enzyme?
MAO (specifically MAO-A)
Catecholamines are derived from what amino acid only?
Tyrosine
What are the 3 Catecholamines?
Dopamine, norepinephrine, epinephrine
Serotonin is a synthesized from what?
Tryptophan
What are the enzymes in the 2 step synthesis of serotonin?
Tryptophan 5 hydroxylase
AAAD
Serotonin is the precursor of what?
Melatonin
All monoamine receptors, except serotonin 5HT-3, belong to what category of receptors?
Metabotropic GPCR
What is a diamine that is located in the tuberomamillary nucleus of the hypothalamus and increase the state of arousal, synthesized from histidine by histidine decarboxylase and metabolized by histidine methyltransferase (HMT)?
Histidine
What are 3 examples of purinergic neurotransmitters in the brain?
ATP, UTP, adenosine
What neurotransmitter is present in synaptic vesicles with other classical neurotransmitters, is co released during synaptic transmission, binds own receptor but also is converted to UTP and adenosine by enzymes which bind their appropriate receptors?
ATP
What transport nucleoside analogs that act as therapeutic drugs for the treatment of cancer or AIDS (AZT)?
Nucleoside transporters
What type of purinergic receptors are inhibitory in the CNS and are responsible for anxiolytic, anticonvulsant, analgesic and sedative actions?
A1 (adenosine 1) receptors
What is highly expressed in the dorsal striatum, nucleus accumbens, and olfactory tubercle, in the striatum this receptor antagonizes the effect of dopamine D2 receptors, contributes to vasodilation?
A2A
What receptors are present in the endothelial cells, regulate vascular permeability, and contribute to vasodilation?
A2B
Adenosine produces vasodilation and dipryridamole, an inhibitor of adenosine does what so that it can be used clinically to induce coronary produce vasodilation?
Increases it’s extracellular levels
Caffeine and other methylxanthines such as theophylline (tea) and theobromine (chocolate) act as stimulants because they have what effect?
Antagonize all adenosine receptors!
