Pharm_21.txt

specific receptors that modulate synaptic transmission

voltage gated and ligand gated.

• Fast: Na
• Slow: K and Ca

ionotropic receptors

• Neurotransmitters
• Non sensitive to membrane voltage

• 1-Receptor binds a neurotransmitter, activates a G protein(beta gamma subunit) which in turn open an ion channel. Microdomain
• 2- modulate voltage gated channels indirectly by release of a diffusible second messenger. Over significant distance.

• 1- calcium: inhibit channel function, presynaptic inhibition
• 2- potassium: Activate post synaptic channels allowing K to enter the neuron. This causes slow inhibition.

G proteins released by binding of neurotransmitter activate an inter-membrane enzyme (ex: adenylyl cyclase) that produces the second messenger (ex: cAMP)

• Ionotropic: brief effect
• metabotropic: tens of seconds to minutes

Intraterminal calcium concentration.

0.5 ms, due to the release process and opening of Ca channels

inhibitory and excitatory of the post synaptic membrane by ionotropic receptors.

The cell is depolarized

• act on pre synaptic terminal to reduce the amount of transmitter released.
• Found mostly in the spinal cord but receptors are on pre synaptic terminals in the brain, though that neighboring neurotransmitters spill out of the synaptic terminal and bind to these receptors. This will inhibit release of neurotransmitter limiting the activation of multiple pathways at one in the brain.

synthesis, storage, metabolism, and release of neurotransmitter

causes the release of catecholamines from adrenergic synapses.

blocks the release of neurotransmitters

causes the release of the peptide substance P from sensory neurons

• taken up by presynaptic terminal and neuroglial cells
• enzimatically destroyed

Ex. block the formation of cAMP to inhibit or block the metabolism of cAMP to prolong AP

• Localization - if the neurotransmitter is in the presynaptic terminal
• Release - is the neurotransmitter in the extracelluar fluid of the area.
• Synaptic mimicry - does the application of the suspected neurotransmitter produce the same response as nerve stimulation.

• 1- Hierarchical system
• 2 - non specific or diffuse.

pathways of sensory and motor control

• 1 - relay or projection. Transmit signals over long distances. excitatory, glutamate
• 2 - local circuit neurons, short distance, inhibitory, GABA or glycine. synapse on cell bodies of projection neurons. Feed back and feed forward pathways.

axon, neurotransmitter is released from the dendrite. they release in a graded fashion without AP stimulus.

Inhibits GABAa receptors ans causes convulsions.

• monoamines - epinaphrine, norepinephrine, serotonin, dopamine
• effects are determined by the location of receptors and not by the release site.
• Act on metatrohic receiptors so have a long lasting effect.

Glutimate is taken up by glial cells and converted to glutamine by glutamine synthetase, glutamine is then released and taken up by presynaptic terminals and converted back to glutamate by glutaminase.

• ionotrophic - 4 subtypes - AMPA, KA, NMDA
• metabotrophic - inhibatory

increases the Ca permeability, excitatory

• heterotetromers made of GluR1-R4
• mostly GluR2
• excitatory, permiable to Na and K

hippocampus, cerebellum, spinal cord

• I- located post synaptically, excitability by activating non specific cation channels.
• II and III are presynaptic and are inhibitory blocking Ca channels and lowering the amount of neurotransmitter released. Only activated when the amount of glutamate rises during repetitive stimulation (self down regulation)

post synaptic density, NMDA in the middle and Ampa at the periphery.

• spinal cord and brain stem
• inhibitory

• GABAa - inotropic, fast receptors, selectivly permiable to Cl
• GABAb - metatropic, slow receptors, coupled to G proteins, mostly located on presynaptic and activated by the spill over of GABA self inhibiting GABA neurotransmitter release. Inhibit adenyly cyclase.

• mediated by a large family of G protein coupled muscarinic receptors
• M1- slow excitation, works opposite of most by decreasing the membrane permeability to K.
• large function in memory by creating long term potentials
• M2 are inhibitory, open K channels.

Nicotinic receptors, opening of fast sodium channels

• dopamine, morepinephrine, seratonin
• cocaine blocks the reuptake of dopamine and norepinethrine

• five subunits or receptors D1-D5
• two classed D1 like D1 and D5
• D2 like D2 D3 D4
• exerts a slow inhibitory action on the CNS, opens K channels

• noradronergic neurons
• matabotropic
• hyperpolorizes neurons by increasing K conductance, mediated by Alpha 2
• can indirectly excite neurons by inhibiting the inhibitory neuron of it.

• pathways originate in the pons and upper brainstem
• metabotropic
• inhibitory through K conductance

excitatory post synaptic potention

pain receptors

• NO is made by nitric oxide synthase NOS.
• NOS is activated by calcium-calmodulin, NMDA receptors increase the amount of Ca in a neuron and increase the amount of NO

• THC effects the brain by activating cannabinoid receptor CB1.
• CB1 endogenous ligands are not stored but synthesized in response to depolarization and Ca influx
• can act retrograde, post synaptic will release and they will bind and inhibit presynaptic. Effect memory, cognitive function, and pain in this mannor.