Neurotransmitters: Difference between revisions

(18 intermediate revisions by the same user not shown)

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~~'''Under construction!!!'''~~

=Acetylcholine=

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==Acetylcholine Receptors==

===Nicotinic acetylcholine receptors===

~~====~~[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]]====

*[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]]

*[[Alpha-bungarotoxin]] is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake ~~belonging to a group commonly known as kraits~~.

The receptor is a transmembrane pentameric glycoprotein. It cylindrical in appearance by electron microscopy approximately 16nm in length and 8nm in diameter. The main ion channel is composed of a water pore that runs through the entire length of the protein. If viewed from the synaptic cleft, the protein will look like a pseudo-symmetrical rosette shown in the picture below composed of 10 different alpha and 4 different beta subunits.

~~====~~[[Binding site of AChR]]~~====~~

*<scene name='58/584302/Cv/1'>Side view</scene>.

~~====~~[[Acetylcholine Receptor and its Reaction to Cobra Venom]]====

*<scene name='58/584302/Cv/2'>View from extracellular side</scene>.

*<scene name='58/584302/Cv/3'>View from cytoplasmic side</scene>.

*[[Alpha-bungarotoxin]] is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake.

*[[Binding site of AChR]]

*[[Acetylcholine Receptor and its Reaction to Cobra Venom]]

When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. The 2nd image depicts an individual toxin binding with one chain on the receptor, both in the same color. <scene name='77/778333/Cobra_snake_venom/3'>Cobra Venom Interaction with Acetylcholine Receptor</scene>. This representation shows each molecule of the <scene name='77/778333/Venom_receptor_piece/1'>Cobra toxin binding to one chain of the receptor</scene>.

===Muscarinic acetylcholine receptors===

[[Muscarinic acetylcholine receptor]]

M1, M3, M5 receptors are coupled with Gq proteins, while M2 and M4 receptors are coupled with Gi/o proteins. They belong to GPCRs Subfamily A18.

*[[Muscarinic acetylcholine receptor]]

==Acetylcholinesterase==

Line 49:

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==Adenosine receptors==

Gs → cAMP up

*[[Adenosine A2A receptor]]

*[[Caffeine|Effect of Caffeine (Trimethylxanthine) on Human A2A Receptor]]

*[[Adenosine A2A receptor 3D structures]]

Agonists:

*N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)

*ATL-146e

*CGS-21680

*Regadenoson

*Adenosine

Antagonists:

*Caffeine

*aminophylline

*theophylline

*istradefylline

*SCH-58261

*SCH-442,416

*ZM-241,385

=Adrenaline (Epinephrine)/Noradrenaline (Norepinephrine)=

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* The β-1 adrenergic receptor (B1AR) increases cardiac output and secretion of rennin and ghrelin.<ref>PMID:23435379</ref>

* The β-2 adrenergic receptor (B2AR) triggers many relaxation reactions.

===~~Beta-~~adrenergic ~~receptors~~===

===β1 adrenergic receptor===

~~====~~[[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]~~====~~

~~====~~[[~~Beta-2 Adrenergic Receptor|Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel~~]]~~====~~

*3D structures in [[Adrenergic receptor]].

~~====[[Beta-2 adrenergic receptor|Article Beta-2 adrenergic receptor by Joel L~~. ~~Sussman, Tala Curry, Michal Harel, Jaime Prilusky]]====~~

*[[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]

~~=====[[Group:SMART:A Physical Model of the beta-Adrenergic Receptor]]=====~~

*Gs: [[adenylate cyclase]] activated, cAMP up.

~~====[[Beta2 adrenergic receptor-Gs protein complex updated]]====~~

~~===[[Adrenergic receptor 3D structures|3D Structures of Adrenergic receptors]]===~~

~~===[[Beta-adrenergic receptor kinase]]===~~

===Monoamine oxidases (MAO)===

*β1-adrenergic agonists:

**Dobutamine, see [[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]], [[2y00]], [[2y01]], [[6h7l]].

**Isoprenaline, see [[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]], [[2y03]].

**Noradrenaline

**Carmoterol, see [[2y02]].

**[[Salbutamol]] (Albuterol in USA), [[2y04]].

*Beta blockers:

**Metoprolol

**Atenolol

**Bisoprolol

**Propranolol

**Timolol

**Nebivolol

**Vortioxetine

===β2 adrenergic receptor===

* The human β2 adrenergic receptor bound to a G-protein ([[3sn6]]) is featured in a scene above, and additional structures are on the [[Adrenergic receptor|Adrenergic receptor page]].

*[[Beta-2 Adrenergic Receptor|Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel]]

*[[Beta-2 adrenergic receptor|Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky]]

*[[Group:SMART:A Physical Model of the beta-Adrenergic Receptor]]

*Gs: adenylate cyclase activated, cAMP up. For Gs see [[Beta2 adrenergic receptor-Gs protein complex updated]].

β2-adrenergic agonists:

**[[Salbutamol]] (Albuterol in USA)

**Bitolterol mesylate

**[[Formoterol]]

**Isoprenaline

**Levalbuterol

**Metaproterenol

**[[Salmeterol]]

**Terbutaline

**Ritodrine

*Beta blockers:

**Butoxamine

**Timolol

**Propranolol

**ICI-118,551

**Paroxetine

==[[Beta-adrenergic receptor kinase]]==

==Monoamine oxidases (MAO)==

Monoamine oxidases (MAO) (EC 1.4.3.4) are a family of enzymes that catalyze the oxidation of monoamines including adrenaline, noradrenaline, serotonin and dopamine.

====[[Monoamine oxidase]]====

===[[Monoamine oxidase]]===

====[[Monoamine oxidase b]]====

===[[Monoamine oxidase b]]===

=Dopamine=

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=GABA=

==GABA receptors==

'''GABA''' (i.e. gamma-aminobutyric acid) is the primary inhibitory neurotransmitter of the vertebrate central nervous system. GABA can bind one of two different receptor proteins, each using a discrete mechanism to elicit a cellular response. Upon binding with GABA, '''GABAB receptors''' (metabotropic) utilize a second messenger amplification pathway that ultimately results in an inhibitory signal for neuronal transmission. This pathway for signal transmission differs from ~~'''~~GABAA receptors~~'''~~ (ionotropic), which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal.

'''GABA''' (i.e. gamma-aminobutyric acid) is the primary inhibitory neurotransmitter of the vertebrate central nervous system. GABA can bind one of two different receptor proteins, each using a discrete mechanism to elicit a cellular response. Upon binding with GABA, '''GABAB receptors''' (metabotropic) utilize a second messenger amplification pathway that ultimately results in an inhibitory signal for neuronal transmission. This pathway for signal transmission differs from [[GABAA receptors]] (ionotropic), which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal.

<scene name='82/829381/Cv/9'>GABA bound to the GABAB receptor</scene> (PDB code [[4ms3]]).

*[[GABA receptor]]

*[[User:Rana Saad/The human GABAb receptor]]

*[[GABAA receptor]]

==[[GABA(A) receptor-associated protein]]==

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*'''NMDA receptor''' (NMDAR) is a IGluR which binds to the agonist NMDA. It contains subuntis NR1, NR2A, NR2B, NR2C, NR2D, NR3A, NR3B.

*[[Ionotropic Glutamate Receptors]]

*[[Molecular Playground/Glutamate Receptor|AMPA glutamate receptor]]

Full view of the glutamate receptor shows the overall structure (N-terminal, ligand-binding and transmembrane domains) in <scene name='User:Mariel_Feliciano/sandbox_1/Full_view_black_background/6'>ribbon</scene> and <scene name='User:Mariel_Feliciano/sandbox_1/Full_view_spacefill/2'>spacefilling</scene> models. <scene name='User:Mariel_Feliciano/sandbox_1/Amino_terminal_domains/2'>N-terminal domain</scene> is a part of the extracellular domain. This domain is implicated in receptor assembly, trafficking, and localization.

*<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains/5'>Transmembrane Domain</scene>.

*<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains_pore2/1'>Transmembrane Domain, other representaion</scene>. This domain widens in response to glutamate binding allowing for positive ions to pass through the post-synaptic membrane.

*<scene name='Molecular_Playground/Glutamate_Receptor/Glu_antagoinist/2'>Receptor antagonist 2K200225 binding site</scene>.

*<scene name='Molecular_Playground/Glutamate_Receptor/Glu_agonist_/2'>Glutamate binding site</scene>.

*[[Glutamate receptor (GluA2)]]

===Metabotropic Glutamate Receptors===

Metabotropic glutamate receptors are [[Glutamate Receptors|glutamate receptors]] that activate ion channels indirectly through a signaling cascade involving G proteins<ref>PMID:20716669</ref>. They are members of the large class of seven-transmembrane domain receptors, the [[G protein-coupled receptor|G protein-coupled receptors]]. Glutamate receptors are classified into 3 groups based on their homology, mechanism and pharmacological properties.

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*[[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]

*[[Metabotropic glutamate receptor 5]]

~~====AMPA receptors====~~

*[[Molecular Playground/Glutamate Receptor]]

=Histamine=

<scene name='82/829381/Cv/5'>Histamine</scene>.

==Histamine receptors==

Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the H1 receptor triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response.

Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the H1 receptor triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response. The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. The H1 receptor is linked to an intracellular G-protein (Gq) that activates [[phospholipase C]] (see [[PLC beta 3 Gq|Unique bidirectional interactions of Phospholipase C beta 3 with G alpha Q]] and the inositol triphosphate (IP3) signalling pathway. When a ligand binds to a G protein-coupled receptor that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG.

*[[Histamine H1 receptor]]

* [[3rze]] - human histamine H1 receptor with an antagonist doxepin.

=Neurotensin=

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Line 206:

The ligand for NTSR1 is the 13 amino acid peptide, neurotensin (NTS)<ref name="SONT">PMID:23051748</ref>, and the majority of the effects of NTS are mediated through NTSR1<ref name="SONT"/>. NTS has a variety of biological activities including a role in the '''[https://en.wikipedia.org/wiki/Leptin leptin]''' signaling pathways <ref name="Mice">PMID: 20211191</ref>, tumor growth <ref name="cancer">PMID:16887236</ref>, and '''[https://en.wikipedia.org/wiki/Dopamine dopamine]''' regulation <ref name="Schizophrenia">PMID:22596253</ref>. NTSR1 was crystallized bound with a C-terminal portion of its tridecapeptide '''[https://en.wikipedia.org/wiki/Ligand ligand]''', <scene name='72/721548/Neurotensin/7'>NTS(8-13)</scene>. The shortened ligand was used because of oits higher potency and efficacy than its full-length counterpart<ref name="SONT"/>.

[[Neurotensin receptor]]

*[[Neurotensin receptor]]

Like other G protein-coupled receptors, NTSR1 is composed of 3 distinct regions. An <scene name='72/727765/Overall_structure/5'>extracellular binding site</scene> where neurotensin binds and causes a conformational change of the protein. A region containing <scene name='73/733990/Overall/1'>7 transmembrane alpha helices</scene> (PDB code:[http://www.rcsb.org/pdb/explore/explore.do?structureId=4GRV 4GRV)] that transduce the signal from the extracellular side of the cell membrane to the intracellular side. Lastly, an intracellular region that when activated by a conformational change in the protein activates a [https://en.wikipedia.org/wiki/G_protein G-protein] associated with this receptor.

The <scene name='72/721547/Hydrophobic_binding_pocket/6'>hydrophobic binding pocket</scene> in NTSR1 is located at the top of the protein (Figure 1). NTSR1 also contains an '''[https://en.wikipedia.org/wiki/Allosteric_regulation allosteric]''' <scene name='72/721548/Na_bind_pocket/13'>sodium binding pocket</scene>, which is located directly beneath the ligand binding pocket and the two pockets, which are separated by the residue <scene name='72/721548/Trp321/1'>Trp321</scene><ref name="SPGP">PMID:26205105</ref>. NTSR1 has been mutated to exist in both <scene name='72/721548/Ntsr1-elf/6'>active</scene> and <scene name='72/721547/Ntsr1-gw5/8'>active-like</scene> states.

=Serotonin=

Neurotransmitters: Difference between revisions

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@@ Line 1: / Line 1: @@
-'''Under construction!!!'''
 <StructureSection load='' size='400' side='right' scene='Acetylcholine/Cv/1' caption=''>
 =Acetylcholine=
@@ Line 6: / Line 5: @@
 ==Acetylcholine Receptors==
 ===Nicotinic acetylcholine receptors===
-====[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]]====
+*[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]]
-*[[Alpha-bungarotoxin]] is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake belonging to a group commonly known as kraits.
+The receptor is a transmembrane pentameric glycoprotein. It cylindrical in appearance by electron microscopy approximately 16nm in length and 8nm in diameter. The main ion channel is composed of a water pore that runs through the entire length of the protein. If viewed from the synaptic cleft, the protein will look like a pseudo-symmetrical rosette shown in the picture below composed of 10 different alpha and 4 different beta subunits.
-====[[Binding site of AChR]]====
+*<scene name='58/584302/Cv/1'>Side view</scene>.
-====[[Acetylcholine Receptor and its Reaction to Cobra Venom]]====
+*<scene name='58/584302/Cv/2'>View from extracellular side</scene>.
+*<scene name='58/584302/Cv/3'>View from cytoplasmic side</scene>.
+*[[Alpha-bungarotoxin]] is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake.
+*[[Binding site of AChR]]
+*[[Acetylcholine Receptor and its Reaction to Cobra Venom]]
+When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. The 2nd image depicts an individual toxin binding with one chain on the receptor, both in the same color. <scene name='77/778333/Cobra_snake_venom/3'>Cobra Venom Interaction with Acetylcholine Receptor</scene>. This representation shows each molecule of the <scene name='77/778333/Venom_receptor_piece/1'>Cobra toxin binding to one chain of the receptor</scene>.
 ===Muscarinic acetylcholine receptors===
-[[Muscarinic acetylcholine receptor]]
+M1, M3, M5 receptors are coupled with G<sub>q</sub> proteins, while M2 and M4 receptors are coupled with G<sub>i/o</sub> proteins. They belong to GPCRs Subfamily A18.
+*[[Muscarinic acetylcholine receptor]]
 ==Acetylcholinesterase==
@@ Line 49: / Line 57: @@
 ==Adenosine receptors==
+G<sub>s</sub> → cAMP up
 *[[Adenosine A2A receptor]]
 *[[Caffeine|Effect of Caffeine (Trimethylxanthine) on Human A2A Receptor]]
+*[[Adenosine A2A receptor 3D structures]]
+Agonists:
+*N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)
+*ATL-146e
+*CGS-21680
+*Regadenoson
+*Adenosine
+Antagonists:
+*Caffeine
+*aminophylline
+*theophylline
+*istradefylline
+*SCH-58261
+*SCH-442,416
+*ZM-241,385
 =Adrenaline (Epinephrine)/Noradrenaline (Norepinephrine)=
@@ Line 61: / Line 85: @@
 *  The β-1 adrenergic receptor (B1AR) increases cardiac output and secretion of rennin and ghrelin.<ref>PMID:23435379</ref><br />
 *  The β-2 adrenergic receptor (B2AR) triggers many relaxation reactions.
-===Beta-adrenergic receptors===
+===β1 adrenergic receptor===
-====[[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]====
-====[[Beta-2 Adrenergic Receptor|Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel]]====
+*3D structures in [[Adrenergic receptor]].
-====[[Beta-2 adrenergic receptor|Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky]]====
+*[[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]
-=====[[Group:SMART:A Physical Model of the beta-Adrenergic Receptor]]=====
+*G<sub>s</sub>: [[adenylate cyclase]] activated, cAMP up.
-====[[Beta2 adrenergic receptor-Gs protein complex updated]]====
-===[[Adrenergic receptor 3D structures|3D Structures of Adrenergic receptors]]===
-===[[Beta-adrenergic receptor kinase]]===
-===Monoamine oxidases (MAO)===
+*β1-adrenergic agonists:
+**Dobutamine, see [[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]], [[2y00]], [[2y01]], [[6h7l]].
+**Isoprenaline, see [[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]], [[2y03]].
+**Noradrenaline
+**Carmoterol, see [[2y02]].
+**[[Salbutamol]] (Albuterol in USA), [[2y04]].
+*Beta blockers:
+**Metoprolol
+**Atenolol
+**Bisoprolol
+**Propranolol
+**Timolol
+**Nebivolol
+**Vortioxetine
+===β2 adrenergic receptor===
+* The human β2 adrenergic receptor bound to a G-protein ([[3sn6]]) is featured in a scene above, and additional structures are on the [[Adrenergic receptor|Adrenergic receptor page]].
+*[[Beta-2 Adrenergic Receptor|Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel]]
+*[[Beta-2 adrenergic receptor|Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky]]
+*[[Group:SMART:A Physical Model of the beta-Adrenergic Receptor]]
+*G<sub>s</sub>: adenylate cyclase activated, cAMP up. For G<sub>s</sub> see [[Beta2 adrenergic receptor-Gs protein complex updated]].
+β2-adrenergic agonists:
+**[[Salbutamol]] (Albuterol in USA)
+**Bitolterol mesylate
+**[[Formoterol]]
+**Isoprenaline
+**Levalbuterol
+**Metaproterenol
+**[[Salmeterol]]
+**Terbutaline
+**Ritodrine
+*Beta blockers:
+**Butoxamine
+**Timolol
+**Propranolol
+**ICI-118,551
+**Paroxetine
+==[[Beta-adrenergic receptor kinase]]==
+==Monoamine oxidases (MAO)==
 Monoamine oxidases (MAO) (EC 1.4.3.4) are a family of enzymes that catalyze the oxidation of monoamines including adrenaline, noradrenaline, serotonin and dopamine.
-====[[Monoamine oxidase]]====
+===[[Monoamine oxidase]]===
-====[[Monoamine oxidase b]]====
+===[[Monoamine oxidase b]]===
 =Dopamine=
@@ Line 100: / Line 162: @@
 =GABA=
 ==GABA receptors==
-'''GABA''' (i.e. gamma-aminobutyric acid) is the primary inhibitory neurotransmitter of the vertebrate central nervous system. GABA can bind one of two different receptor proteins, each using a discrete mechanism to elicit a cellular response. Upon binding with GABA, '''GABAB receptors''' (metabotropic) utilize a second messenger amplification pathway that ultimately results in an inhibitory signal for neuronal transmission. This pathway for signal transmission differs from '''GABAA receptors''' (ionotropic), which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal.
+'''GABA''' (i.e. gamma-aminobutyric acid) is the primary inhibitory neurotransmitter of the vertebrate central nervous system. GABA can bind one of two different receptor proteins, each using a discrete mechanism to elicit a cellular response. Upon binding with GABA, '''GABAB receptors''' (metabotropic) utilize a second messenger amplification pathway that ultimately results in an inhibitory signal for neuronal transmission. This pathway for signal transmission differs from [[GABAA receptors]] (ionotropic), which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal.
 <scene name='82/829381/Cv/9'>GABA bound to the GABAB receptor</scene> (PDB code [[4ms3]]).
 *[[GABA receptor]]
 *[[User:Rana Saad/The human GABAb receptor]]
+*[[GABAA receptor]]
 ==[[GABA(A) receptor-associated protein]]==
@@ Line 115: / Line 178: @@
 *'''NMDA receptor''' (NMDAR) is a IGluR which binds to the agonist NMDA.  It contains subuntis NR1, NR2A, NR2B, NR2C, NR2D, NR3A, NR3B.<br />
 *[[Ionotropic Glutamate Receptors]]
+*[[Molecular Playground/Glutamate Receptor|AMPA glutamate receptor]]
+Full view of the glutamate receptor shows the overall structure (N-terminal, ligand-binding and transmembrane domains) in <scene name='User:Mariel_Feliciano/sandbox_1/Full_view_black_background/6'>ribbon</scene> and <scene name='User:Mariel_Feliciano/sandbox_1/Full_view_spacefill/2'>spacefilling</scene> models. <scene name='User:Mariel_Feliciano/sandbox_1/Amino_terminal_domains/2'>N-terminal domain</scene> is a part of the extracellular domain. This domain is implicated in receptor assembly, trafficking, and localization.
+*<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains/5'>Transmembrane Domain</scene>.
+*<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains_pore2/1'>Transmembrane Domain, other representaion</scene>. This domain widens in response to glutamate binding allowing for positive ions to pass through the post-synaptic membrane.
+*<scene name='Molecular_Playground/Glutamate_Receptor/Glu_antagoinist/2'>Receptor antagonist 2K200225 binding site</scene>.
+*<scene name='Molecular_Playground/Glutamate_Receptor/Glu_agonist_/2'>Glutamate binding site</scene>.
 *[[Glutamate receptor (GluA2)]]
 ===Metabotropic Glutamate Receptors===
 Metabotropic glutamate receptors are [[Glutamate Receptors|glutamate receptors]] that activate ion channels indirectly through a signaling cascade involving G proteins<ref>PMID:20716669</ref>. They are members of the large class of seven-transmembrane domain receptors, the [[G protein-coupled receptor|G protein-coupled receptors]]. Glutamate receptors are classified into 3 groups based on their homology, mechanism and pharmacological properties.
@@ Line 121: / Line 192: @@
 *[[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]
 *[[Metabotropic glutamate receptor 5]]
-====AMPA receptors====
-*[[Molecular Playground/Glutamate Receptor]]
 =Histamine=
 <scene name='82/829381/Cv/5'>Histamine</scene>.
 ==Histamine receptors==
-Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the H1 receptor triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response.
+Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the H1 receptor triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response. The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. The H1 receptor is linked to an intracellular G-protein (G<sub>q</sub>) that activates [[phospholipase C]] (see [[PLC beta 3 Gq|Unique bidirectional interactions of Phospholipase C beta 3 with G alpha Q]] and the inositol triphosphate (IP3) signalling pathway. When a ligand binds to a G protein-coupled receptor that is coupled to a G<sub>q</sub> heterotrimeric G protein, the α-subunit of G<sub>q</sub> can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG.
 *[[Histamine H1 receptor]]
+* [[3rze]] - human histamine H1 receptor with an antagonist doxepin.
 =Neurotensin=
@@ Line 136: / Line 206: @@
 The ligand for NTSR1 is the 13 amino acid peptide, neurotensin (NTS)<ref name="SONT">PMID:23051748</ref>, and the majority of the effects of NTS are mediated through NTSR1<ref name="SONT"/>. NTS has a variety of biological activities including a role in the '''[https://en.wikipedia.org/wiki/Leptin leptin]''' signaling pathways <ref name="Mice">PMID: 20211191</ref>, tumor growth <ref name="cancer">PMID:16887236</ref>, and '''[https://en.wikipedia.org/wiki/Dopamine dopamine]''' regulation <ref name="Schizophrenia">PMID:22596253</ref>. NTSR1 was crystallized bound with a C-terminal portion of its tridecapeptide '''[https://en.wikipedia.org/wiki/Ligand ligand]''', <scene name='72/721548/Neurotensin/7'>NTS(8-13)</scene>. The shortened ligand was used because of oits higher potency and efficacy than its full-length counterpart<ref name="SONT"/>.
-[[Neurotensin receptor]]
+*[[Neurotensin receptor]]
+Like other G protein-coupled receptors, NTSR1 is composed of 3 distinct regions. An <scene name='72/727765/Overall_structure/5'>extracellular binding site</scene> where neurotensin binds and causes a conformational change of the protein. A region containing <scene name='73/733990/Overall/1'>7 transmembrane alpha helices</scene> (PDB code:[http://www.rcsb.org/pdb/explore/explore.do?structureId=4GRV 4GRV)] that transduce the signal from the extracellular side of the cell membrane to the intracellular side. Lastly, an intracellular region that when activated by a conformational change in the protein activates a [https://en.wikipedia.org/wiki/G_protein G-protein] associated with this receptor.
+The <scene name='72/721547/Hydrophobic_binding_pocket/6'>hydrophobic binding pocket</scene> in NTSR1 is located at the top of the protein (Figure 1). NTSR1 also contains an '''[https://en.wikipedia.org/wiki/Allosteric_regulation allosteric]''' <scene name='72/721548/Na_bind_pocket/13'>sodium binding pocket</scene>, which is located directly beneath the ligand binding pocket and the two pockets, which are separated by the residue <scene name='72/721548/Trp321/1'>Trp321</scene><ref name="SPGP">PMID:26205105</ref>. NTSR1 has been mutated to exist in both <scene name='72/721548/Ntsr1-elf/6'>active</scene> and <scene name='72/721547/Ntsr1-gw5/8'>active-like</scene> states.
 =Serotonin=