Physiology Lecture 2 (Receptors, GPCRs)

Receptors

These things allow cells to sense what is happening in their environment and respond to that environment, usually is a harsh environment

Hormones, Neurotransmiters, Metabolic Signals

receptors can respond to these examples of specific signal molecules in the cellular environment

Channel receptors

this type of receptor us usually for fast response actions, and operate by having a ligand bind to the receptor, allowing pores of the thing to open, causing ions to flow into the cell. Example is nAChR

G-Protein Coupled Receptors (GPCRs)

this type of receptor that is slow acting and long lasting, and operates by having the agonist bind to the receptor, activiting the protein, which causes the generation of a second messenger, ultimately resulting in the cascade pathway. An example of these is Beta receptors

Tyrosine Kinase Receptors

this type of receptor is slow acting and long lasting, and operates by having the agonist bind to the molecule, causing self dimerization, allowing the molecule to phosphorylate itself resulting in the cascade pathway. Example of these is the insulin receptor

Nuclear Receptors

this type of receptor operates by having the agonist go directly through the cell membrane, and transports to the nucleus, which causes some sort of transcription or translation within the cell. An example of this is a cortisol receptor

Agonist

a molecule that binds to a receptor that causes a stimulatory response

Antagonist

a molecule that binds to a receptor that causes an inhibitory response

Ionotropic

this is another name for a Channel receptor

Metabotropic

this is another name for G protein coupled receptors (GPCRs)

Sodium, Potassium

these ions when flowing through an ion channel are relatively benign and excite the cell when released, usually causing a fast short term effect

Calcium

this ion flows through an ion channel and is more dangerous than the others, and can cause a long lasting effect (ex being NMDA receptors)

Chlorine

this is the only anion that is found in ion channel receptors, and inhibits the excitability of a cell

fast, one, short, slow, many, long

The main difference between Channel Receptors and GPCR receptors is that channel pathway speed is _________, happens via ________ step(s), causing a _________ term effect, and GPCR pathway speed is ________, happens via ________ step(s), and causes a _______ term effect

False, it depends on the type of GPCR (ex. Gs or Gi protein)

True or false, GPCRs can only stimulate a cell

Drugs

in the practical world, GPCRs are important because they are the target to many _______ prescribed

Orphan GPCR

a name for a GPCR in which we do not know the agonist or antagonist

Light

this physical cue causes the cis retinal to transform into the trans retinal, allowing rhodopsin to be activated in the retina of the eye

Mechanical force

this physical cue causes the lipid membrane arangement to be altered, causing the GPCR structure to change in the membrane, activating the receptor

7

this is how many transmembrane helices there are

outside

the N terminus of the GPCR is located __________ of the cell

inside

the C terminus of the GPCR is located ___________ of the cell

C3

this intracellular loop of a GPCR is what interacts with the G proteins

True, as long as they are accessible

True or False, ligand binding sites (agonists or antagonists) can be anywhere on the GPCR

alpha, beta, gamma

the three subunits of a G protein

RGS

this can regulate G protein signaling by inhibiting it

Inactive, GDP

when the G protein is in the __________ state, the alpha, beta, and gamma subunits are all together attached to _________

GDP, GTP, GTP, Alpha, Beta, Gamma

when the GPCR is activated, the ______ is exchanged for _________, causing the G protein to fall apart into two pieces: one consisting of ________ and the ______ subunit, and another consisting of the ________ and __________ subunits

GTP-alpha subunit complex

this piece of the active state G protein is vital to cause the cascading pathway

water, GTP, GDP

when deactivated, ________ phosphorylizes ______ into _______, causing the whole G protein to exist again

RGS exchanges GTP/GDP on the alpha, Agonist dissociates from the receptor, GPCR-agonist complex completely removes itself from membrane

what are the 3 ways that the GPCR can be deactivated?

Gs protein

this type of G protein stimulates the production of cAMP

epinephrine (adrenaline), ADH, TSH

these hormones work through the Gs pathway

GDP, GTP, GTP-alpha subunit, adenylyl cyclase, cAMP

In a Gs type stimulation, the ligand binds to the GPCR, causing the _______ to exchange for _______, breaking the protein apart into two parts, then the ___________ complex binds to _____________, which makes _____________

cAMP, PKA, catalytic, regulatory, catalytic

after cAMP is made by adenyl cyclase, ________ binds to inactive _______ protein, allowing the _______ subunit of it to separate from the __________ subunit of it, allowing the __________ subunit to phosphorylate various molecules for metabolic reasons in the liver

PKA

this protein (when activated), can activate PhosK in order to change metabolic status, can open the L-Ca2+ channel, and can activate the CNGC channel as well, activated by a series of interactions starting with the GPCR from the Gs protein

PDE (phosphodiesterase)

this can break down cAMP to inhibit its effects via hydrolyzation

Gi protein

this G protein type targets the GPCR in order to inhibit the adenylyl cyclase, eventually reducing cAMP levels

Somatostatin, Cannabinoids, ACh

these molecules utlize the Gi protein pathway

stimulating, make, inhibits, stop making

Gi protein GPCRs utilize a similar mechanism as Gs proteins, except instead of __________ adenylyl cyclase to ___________ cAMP, it __________ adenylyl cyclase to __________ cAMP

ion channels

the beta-gamma subunit complex can bind to these when separated from the alpha-GTP complex

Gq protein

this type of GPCR leads to the increased levels of IP3 and DAG (both lipids). Examples of systems that use this are the apha-1 adrenergic receptors in smooth muscle and the histamine 1 receptors in epithelial cells

Calcium

IP3 (inositol triphosphate) leads to the release of internal stores of this ion

protein kinase C (PKC)

DAG (diacyclglyceride) leads to the activaiton of this protein

PLC (phospholipase C), IP3, Calcium, DAG, PKC

Gq pathway is similar to the other GPCRs, except instead of binding to adenylyl cyclase, the GTP-alpha subunit complex binds to ________, which can release ______ causing the release of _________ ions. It can also activate ________ which activates the protein ______

Alzheimer's Disease

muscarinic 1 receptors use the Gq protein pathway to increase the activity to improve neuron survival to alleviate symptoms for this disease

Muscle Inflammation

histamine 1 receptors use the Gq protein pathway which leeads to the release of vasodilators and relaxes smooth muscle in order to relieve this problem

Orthosteric agonist (OA)

this type of agonist binds at the same site as the original agonist, acting as the original agonist to stimulate the GPCR

Allosteric agonist (AA)

this agonist binds at a DIFFERENT binding site from the agonist, but allows the agonist to better bind to the GPCR binding site

Inverse agonist

this type of agonist reduces the basal levels of GPCR activation (for hyperactive GPCRs)

Competitive antagonist (CAnt)

this type of antagonist binds at the same site as the agonist but does not activate the GCPR, thus preventing the agonist from binding

Allosteric antagonist (AAnt)

this type of antagonist binds at a different site than the agonist, but reduces the agonist binding, thus making it difficult for the agonist to bind to its binding site