Amino Acid + Peptide Trasmitters And Nitric Oxide Flashcards
Amino acid neurotransmitters
Predominant type of NT
Up to 90% synapses involve glutamate, GABA, glycine
Excitatory or inhibitory (depending on AA)
Most use ion channel receptors; some metabotropic receptors (i.e. GCPR)
Glutamate
Major excitatory NT
Widely distributed in CNS (vs. Aspartate with more limited distribution)
Classes of ionotropic glutamate receptors
NMDA
Kainate
Kainate-Quisqualate-A (AMPA)
Characteristics of ionotropic glutamate receptors
Heteromeric proteins with 5 subunits
Glutamate-activated catio channels
activated by glutamate
Permeable to Na/K
Excitatory
Excitotoxicity hypothesis
Too much neuronal depolarization > cell death
Too much glutamate > cell death
Immediate effect via necrosis (osmotic swelling > cell lysis)
Delayed effect via apoptosis (sustained NMDA activation > initiate apoptosis)
Glutamate inactivation
Rapid reuptake mechanism (into presynaptic neuron/neighboring glia cells) by Excitatory amino acid transporters (EAATs) powered by electrochemical gradient (Na/K)
Glutamate channels in ischemia
Interruption of blood flow in brain (stroke, heart attack) > collapse of membrane potential > massive release of glutamate + prolonged NMDA activation
Drugs target PCP binding site or glycine bind site to try to reduce cell death
Domoic acid
Toxin in marine algae > accumulates in shellfish/crabs/marine animals > agonist for kainate receptors > headache/confusion/muscle weakness/coordination deficits
Poisoning in sea mammals/sea birds
GABA
Major inhibitory neurotransmitter in CNS
Widely distributed through CNS (inhibitory control of interneurons)
Synthesized from glutamate by GAD (glutamic acid decarboyxlase) ** note a neuron only uses GABA or glutamate (not both)
No toxic effect of GABA
Families of GABA receptor
GABA-A (allow Cl ions into neuron > hyperpolarization)
GABA-B (GPCR connected to K channels > hyperpolarization)
GABA-a receptors acted on by …
Benzodiazepines + barbiturates
These enhance GABAa currents > accentuating inhibtory actions
Increase time/probability of opening channel > more hyperpolarization > more inhibition
Sedative-hypnotic anxiolytics - barbiturates
sodium Amytal, pentobarbital, phenobarbital
Use: sedation, anesthesia, seizure control
Drawbacks: cognitive side effects (confusion, impaired judgement, slowed reflexes); lethal at high doses; tolerance; withdrawal; easily abused
Sedative-hypnotic anxiolytics - benzodiazepines
Diazepam, alprazolam
Low incidence of tolerance, less severe withdrawal, can target anxiety without sedation
Short acting - anxiolytics
Long lasting - anxiolytics, muscle relaxants, anti-convulsants
