Neurotransmitters and other chemical signalling agents


Small-molecule neurotransmitters

Acetylcholine (ACh)

Precursors:Choline and acetyl-CoA
Synthesising enzymes:Choline acetyl transferase
Metabolising enzymes:Acetylcholinesterase
Metabolite:Choline and acetate
Receptor subtypesAgonistsAntagonistsSecond messenger
M1 muscarinicMethacholinePirenzepine,
telenzepine
PI
M2MethacholineHimbacine,
methoctramine
(-ve)cAMP, (+ve)gK+
M3MethacholineHexahydrosila-
difenidol
PI
M4
M5 MB
MethacholineTropicamide(-ve)cAMP
PI
Nicotinic
(neuronal/
ganglion type)
Dimethylphenyl-
piperazinium,
nicotine
mecamylamine,
hexamethonium
((+)tubocurarine
blocks channel)
(+ve)g(cation)
Nicotinic
(muscle type)
Suxamethonium
(also causes
depolarisation
block)
alpha-bungarotoxin,
(+)tubocurarine
(decamethonium
blocks channel)
(+ve)g(cation)

Adenosine (P1 purinoceptors)

Precursors:Mainly AMP (from released ATP)
Synthesising enzymes:Mainly 5'-nucleotidase
Metabolising enzymes:Adenosine deaminase
Metabolite:Inosine
Receptor subtypesAgonistsAntagonistsSecond messenger
A1CPA, R-PIA,
GR 79236
8PT, DPCPX(-ve)cAMP
A2ACGS21680,
CV-1808
8PT, CGS 15943(+ve)cAMP
A2BMetrifudil8PT(+ve)cAMP
A3 MBR-PIA, NECAnone(-ve)cAMP

ATP (P2 purinoceptors)

Precursors:Normal cellular constituent; formed from ADP
Synthesising enzymes: Phosphorylases
Metabolising enzymes:Phosphatases
Metabolites: ADP, AMP, adenosine, inosine
Receptor subtypesAgonistsAntagonistsSecond messenger
P2Xbeta-gamma-Me-ATPalpha-beta-Me-ATP
(desensitises)
suramin
(+ve)g(cation) or
(up)gCa2+
P2YADP-beta-F,
2-Me-S-ATP
Reactive blue 2,
suramin
PI, (+ve)gK
P2T (platelet)ADPSuramin, AMP(-ve) cAMP,
(+ve)g(cation)
P2Z
(mast cell)
ATP4-none?
P2UUTPnonePI

Monoamines (biogenic amines)

Norepinephrine (Noradrenaline; NA) and Epinephrine (Adrenaline; AD)

Precursors:L-Tyrosine (a) -> L-DOPA
(b) -> dopamine
(c) -> noradrenaline
(d) -> adrenaline
Synthesising enzymes:(a) tyrosine hydroxylase,
(b) L-aromatic amino-acid decarboxylase,
(c) dopamine-beta-hydroxylase,
(d) phenylethanolamine-N-methyl transferase
Metabolising enzymes:MAO and COMT
Metabolites:Vanillylmandelic acid (VMA) and
3-methoxy-4-hydroxyphenylglycol (MHPG)
Receptor subtypesAgonistsAntagonistsSecond messenger
alpha(1A)PhenylephrinePrazosin,
(+)-niguldipine
PI
alpha(1B)PhenylephrinePrazosin, CEC PI
alpha(1C)PhenylephrinePrazosin, CEC PI
alpha(2A)OxymetazolineYohimbine,
fluparoxan
(-ve)cAMP,
(down)gCa(2+),
(down)gK+
alpha(2B)UK14304Prazosin, ARC 239(-ve)cAMP,
(down)gCa(2+)
alpha(2C)UK14304Yohimbine(-ve)cAMP
beta(1)Xamoterol,
RD363
Practolol,
atenolol,
CGP20712A
(+ve)cAMP
beta(2)Salbutamol, salmeterol,
procaterol
ICI 118551(+ve)cAMP
beta(3)BRL 37344
BRL 35135
cyanopindolol(+ve)cAMP

Dopamine (DA)

Precursors:Tyrosine (a) -> L-dihydroxyphenylalanine (L-DOPA)
(b) -7gt; dopamine
Synthesising enzymes: (a) Tyrosine hydroxylase;
(b) L-aromatic amino-acid decarboxylase (DOPA decarboxylase)
Metabolising enzymes:MAO and catechol-O-methyl transferase (COMT)
Metabolite: 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
Receptor subtypesAgonistsAntagonistsSecond messenger
D1SKF 38393Sch 23390(+ve) cAMP
D2QuinpiroleSulpiride(+ve)gK+
D37-OH-DPATAJ-76?
D4DopamineClozapine?
D5DopamineSch 23390(+ve)cAMP

5-Hydroxytryptamine (5-HT; serotonin)

Precursors:Tryptophan (a) -> 5-hydroxytryptophan
(b) -> 5HT
Synthesising enzymes: (a) Tryptophan hydroxylase,
(b) 5HTP decarboxylase
Metabolising enzymes:Monoamine oxidase (MAO)
Metabolite:5HIAA
Receptor subtypesAgonistsAntagonistsSecond messenger
5HT(1A)8-OH-DPATWay 100135,
SDZ 216-525
(-ve) cAMP
5HT(1B)CP 93129Cyanopindolol(-ve) cAMP
5HT(1C) now re-classified as 5HT(2C)
5HT(1D)5CT, sumatriptanMethiothepin,
methysergide
(-ve) cAMP
5HT(1D-alpha) MB
5HT(1DB) MB (human homologue of the rodent 5HT1B receptor)
5HT(1E-alpha) MB(-ve) cAMP
5HT(1EB) MB(-ve) cAMP
5HT(1F) MB(-ve) cAMP
5HT(2A)
(old 5HT(2))
DOIKetanserinPI
5HT(2B)
(rat fundus)
DOIKetanserinPI
5HT(2C)
(old 5HT1C)
mCPPMesulerginePI
5HT(3)2-Me-5HTOndansetron,
granisetron
(+ve)g(cation)
5HT(4)5MeOTrp,
cisapride
GR 113808(+ve)cAMP
5HT(5) MB(binds bufotenine)

Histamine (HA)

Precursors:Histidine
Synthesising enzymes:Histidine decarboxylase
Metabolising enzymes:Histamine-N-methyl transferase, histaminase, etc.
Metabolite:Methylhistamine, IAA and others
Receptor subtypesAgonistsAntagonistsSecond messenger
H(1)2-thiazolyl-
ethylamine
MepyraminePI
H(2)DimapritRanitidine,
cimetidine
(+ve)cAMP
H(3)(R)-alpha-methyl
histamine
Thioperamide?

Excitatory amino acids (EAA)

Glutamate (Glu) (and Aspartate)

Precursors:None
Synthesising enzymes:None
Metabolising enzymes:Glutamate transaminase (uptake is more important)
Metabolite:Glutamine
Receptor subtypesAgonistsAntagonistsSecond messenger
NMDA
(subtypes MB)
NMDA, AP5,
CPP
CGP37849 (MK801
is a channel
blocker, PCP
is non-competitive)
(+ve)g(cation)
AMPA
(subtypes MB)
AMPA, quisqualateNBQX, NQX
DNQX
(+ve)g(cation)
Kainate
(subtypes MB)
Kainate, domoate NBQX, NQX
DNQX
(+ve)g(cation)
Metabotropic
(subtypes MB)
1S,3R-ACPD,
ibotenate
NonePI

Inhibitory amino acids (IAA)

gamma-Aminobutyric Acid (GABA)

Precursors:Glutamate
Synthesising enzymes: Glutamic acid decarboxylase (GAD)
Metabolising enzymes:GABA transaminase
Metabolite: Succinic semialdehyde
Receptor subtypesAgonistsAntagonistsSecond messenger
GABAAMuscimol, THIP,
isoguvacin
Bicuculline,
picrotoxin
(+ve)gCl
GABABBaclofen,
CGP 97541
2-OH-Saclofen,
CGP 35348
(-ve)gK+, (-ve)gCa2+,
(-ve)cAMP
Benzodiazepine
site on GABAA
receptor
Diazepam (DMCM
is an inverse
agonist)
FlumazenilEnhances
(+ve)gCl- by GABA

Glycine (Gly)

Precursors:None
Synthesising enzymes:None
etabolising enzymes:None (uptake is more important)
Metabolite:None
Receptor subtypesAgonistsAntagonistsSecond messenger
GlycineGlycineStrychnine(+ve)gCl-
Allosteric site
on NMDA receptor
Glycine7-chloro-kynurenaten/a

Large-molecule neurotransmitters (neuropeptides) and other substances

Angiotensin II (AT II)

Precursors:Angiotensin I
Synthesising enzymes:Angiotensin converting enzyme (ACE)
Metabolising enzymes:Aminopeptidase
Metabolite:Angiotensin III
Receptor subtypesAgonistsAntagonistsSecond messenger
AT1Angiotensin II,IIILosartan
(DuP753),
GR 117289
PI, (-ve)cAMP
AT2 Angiotensin II,IIIPD 123177,
PD 123319,
CGP42112
(-ve)cGMP

Bradykinin (BK)

Precursors:Kininogens
Synthesising enzyme:Kallikrein
Metabolising enzyme:ACE, kininase I (carboxypeptidase-N)
Metabolites:Des-Arg9-bradykinin, other fragments
Receptor subtypesAgonistsAntagonistsSecond messenger
B1Des-Arg9-BKDes-Arg9,
Leu8-BK
Des-Arg10-HOE140
?
B2Hyp9,Tyr(Me)8-BKNPC567, HOE140,
NPC349
PI

Cholecystokinin (CCK) (and Gastrin (G))

Precursors:Preprocholecystokinin
Synthesising enzymes: Post-translational peptidases
Metabolising enzymes:Endopeptidase EC 24:11
Metabolite:Peptide fragments
Receptor subtypesAgonistsAntagonistsSecond messenger
CCK(A)A71378Devazepide,
lorglumide
PI
CCK(B)CCK4L365260,
PD134308
?
Gastrin *G17L365260PI
* may be identical to CCK(B)

Enkephalin (met- and leu-) and Dynorphin

Precursors:Proenkephalin and prodynorphin
Synthesising enzymes: Peptidases
Metabolising enzymes: Enkephalinase (EC 24:11) and other peptidases
Metabolite: Peptide fragments
Receptor subtypesAgonistsAntagonistsSecond messenger
µ-opoidDAGOL (DAMGO)Naloxone(-ve)cAMP, (+ve)gK+
delta-opoidDPDPENaltrindol(-ve)cAMP, (+ve)gK+
kappa-opoidU69593, CI 977,
dynorphin
Norbinaltorphimine(-ve)gCa2+

Endothelin (ET)

Precursors:preproET-1 etc.
Synthesising enzymes:"endothelin converting enzyme"
Metabolising enzymes:not known
Receptor subtypesAgonistsAntagonistsSecond messenger
ET(A)ET-1, ET-2FR139317, BQ123PI
ET(B)Sarafotoxin S6C,
[Ala(1),(3),(11),(15)] ET-1,
BQ 3020
IRL 1038 PI
ET(C) MB

Nitric Oxide (NO; formerly EDRF)

Precursors:L-arginine
Synthesising enzymes:NO synthase
Metabolising enzymes:none: diffusion and spontaneous breakdown
Metabolite:NO(2)-, NO(3)-
NO has no conventional receptor, but it activates guanylate cyclase directly. It can be generated by glyceryl trinitrate or sodium nitroprusside. The synthetic enzyme can be inhibited by L-NMMA and L-NAME. Three NO synthases have been cloned, of which one (in macrophages) is\inducible, and two (in brain and endothelium) are constitutive.

Prostanoids (Prostaglandins, prostacyclin and thromboxane)

Precursors:rachidonic acid (i.e. eicosatetraenoic acid;
2-series prostanoids), eicosatri- and
eicosapentaenoic acids
Synthesising enzymes: Prostaglandin synthetase (cyclooxygenase),
PGI2 synthase, TX synthase.
Metabolising enzymes:15-hydroxyprostaglandin dehydrogenase,
PG-9-keto-reductase
Metabolites: large number of oxidised metabolites
Receptor subtypes
(most potent natural prostanoid)
AgonistsAntagonistsSecond messenger
DP (PGD(2))BW245C, ZK110841BWA868C, AH6809<87>cAMP
EP (PGE(2)), subdivided as shown:
EP(1)sulprostone, iloprostAH6809, SC-19220PI
EP(2)AY23626, butaprost,
rioprostil
none<87>cAMP
EP(3)sulprostone
AY23626, rioprostil,
enprostil, GR 63799
nonePI, <51>cAMP
FP (PGF(2-alpha))fluprostenol,
cloprostenol
nonePI
IP (PGI(2))iloprost,cicaprostnone<87>cAMP
TP (TXA(2)) U-46619, STA2,
EP171
GR32191, EP092,
BM13505, SQ28668
PI

Substance P (SP) and Neurokinins A and B (NKA, NKB)

Precursors:Preprotachykinins
Synthesising enzymes: Peptidases
Metabolising enzymes:ACh-esterase, EC 24.11
Metabolite:Peptide fragments
Receptor subtypesAgonistsAntagonistsSecond messenger
NK(1) SPOMe, GR 73632,
Sar9Met(O2)11SP
GR82334, RP67580,
CP-99994
PI
NK(2)GR 64349L-659877, SR48968,
MEN10207, GR94800
GR100679
PI
NK(3)SenktideGR138676PI

Other neurotransmitter substances

NeurotransmitterAbbreviation
Antidiuretic hormone (vasopressin)ADH
Atrial natriuretic peptideANP or ANF
Bombesin
Calcitonin-gene-related peptideCGRP
Corticotrophin-releasing factorCRF
Galanin--
LeukotrieneLT
Luteinising hormone releasing hormoneLHRH
Melatonin--
Neuropeptide YNPY
Neurotensin NT
Oxytocin--
Pancreatic polypeptide (human)(h)PP
Peptide YYPYY
Platelet aggregating factorPAF
Somatostatin SS or SRIF
Taurine--
Thyrotropin-releasing hormoneTRH
Vasoactive intestinal polypeptideVIP

NB: (+ve) indicates increase; (-ve) indicates decrease.


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