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)
