Neurotransmitters: Difference between revisions

(12 intermediate revisions by the same user not shown)

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

=Acetylcholine=

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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]]====~~

~~====[[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]]=====~~

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

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

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

===Monoamine oxidases (MAO)===

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

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

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

*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 receptor]]

*[[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]]

=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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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 86: / 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]]====
-====[[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]]=====
-====[[Beta2 adrenergic receptor-Gs protein complex updated]]====
-===[[Adrenergic receptor 3D structures|3D Structures of Adrenergic receptors]]===
-===[[Beta-adrenergic receptor kinase]]===
-===Monoamine oxidases (MAO)===
+*3D structures in [[Adrenergic receptor]].
+*[[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]
+*G<sub>s</sub>: [[adenylate cyclase]] activated, cAMP up.
+*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 125: / 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 140: / 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 receptor]]
+*[[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 147: / Line 192: @@
 *[[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]
 *[[Metabotropic glutamate receptor 5]]
 =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 161: / 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=