Neuropeptide Y receptor

Neuropeptide Y receptors are a family of receptors belonging to class A G-protein coupled receptors and they are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide.^[1] These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety.^[2]^[3]^[4]^[5]^[6]^[7]

Activated neuropeptide receptors release the G_i subunit from the heterotrimeric G protein complex. The G_i subunit in turn inhibits the production of the second messenger cAMP from ATP.

Only the crystal structure of Y1 in complex with two antagonist is available.^[8]

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Types

There are five known mammalian neuropeptide Y receptors designated Y₁ through Y₅.^[9] Four neuropeptide Y receptors each encoded by a different gene have been identified in humans, all of which may represent therapeutic targets for obesity and other disorders.^[10]^[11]^[12]

Y₁ - NPY1R
Y₂ - NPY2R
Y₄ - PPYR1
Y₅ - NPY5R

Antagonists

References

^ Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T (March 1998). "XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors". Pharmacol. Rev. 50 (1): 143–50. PMID 9549761.
^ Heilig M (August 2004). "The NPY system in stress, anxiety and depression". Neuropeptides. 38 (4): 213–24. doi:10.1016/j.npep.2004.05.002. PMID 15337373. S2CID 37034137.
^ Harro J (October 2006). "CCK and NPY as anti-anxiety treatment targets: promises, pitfalls, and strategies". Amino Acids. 31 (3): 215–30. doi:10.1007/s00726-006-0334-x. PMID 16738800. S2CID 2017793.
^ Eaton K, Sallee FR, Sah R (2007). "Relevance of neuropeptide Y (NPY) in psychiatry". Current Topics in Medicinal Chemistry. 7 (17): 1645–59. doi:10.2174/156802607782341037. PMID 17979774.
^ Xapelli S, Agasse F, Ferreira R, Silva AP, Malva JO (November 2006). "Neuropeptide Y as an endogenous antiepileptic, neuroprotective and pro-neurogenic peptide". Recent Patents on CNS Drug Discovery. 1 (3): 315–24. doi:10.2174/157488906778773689. PMID 18221213.
^ Vona-Davis LC, McFadden DW (2007). "NPY family of hormones: clinical relevance and potential use in gastrointestinal disease". Current Topics in Medicinal Chemistry. 7 (17): 1710–20. doi:10.2174/156802607782340966. PMID 17979780.
^ Lindner D, Stichel J, Beck-Sickinger AG (September 2008). "Molecular recognition of the NPY hormone family by their receptors". Nutrition (Burbank, Los Angeles County, Calif.). 24 (9): 907–17. doi:10.1016/j.nut.2008.06.025. PMID 18725086.
^ Yang Z, Han S, Keller M, Kaiser A, Bender BJ, Bosse M, Burkert K, Kögler LM, Wifling D, Bernhardt G, Plank N, Littmann T, Schmidt P, Yi C, Li B, Ye S, Zhang R, Xu B, Larhammar D, Stevens RC, Huster D, Meiler J, Zhao Q, Beck-Sickinger AG, Buschauer A, Wu B (April 2018). "1 receptor". Nature. 556 (7702): 520–524. doi:10.1038/s41586-018-0046-x. PMC 5920736. PMID 29670288.
^ Larhammar D, Salaneck E (2004). "Molecular evolution of NPY receptor subtypes". Neuropeptides. 38 (4): 141–51. doi:10.1016/j.npep.2004.06.002. PMID 15337367. S2CID 43696257.
^ Kamiji MM, Inui A (October 2007). "Neuropeptide y receptor selective ligands in the treatment of obesity". Endocrine Reviews. 28 (6): 664–84. doi:10.1210/er.2007-0003. PMID 17785427.
^ MacNeil DJ (2007). "NPY Y1 and Y5 receptor selective antagonists as anti-obesity drugs". Current Topics in Medicinal Chemistry. 7 (17): 1721–33. doi:10.2174/156802607782341028. PMID 17979781.
^ Kamiji MM, Inui A (2007). "NPY Y2 and Y4 receptors selective ligands: promising anti-obesity drugs?". Current Topics in Medicinal Chemistry. 7 (17): 1734–42. doi:10.2174/156802607782340957. PMID 17979782.

External links

"Neuropeptide Y Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2007-10-25.
Neuropeptide+Y+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3
Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)
Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)
Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 1 2 FPRL1 OXE Prostaglandin DP (1 2), EP (1 2 3 4), FP Prostacyclin Thromboxane
Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide

B/W (1
2)
FF (1
2)
S
Y (1
2
4
5)
Neuromedin (B
U (1
2))
Neurotensin (1
2)

Other

Anaphylatoxin (C3a
C5a (1
2))
Angiotensin (1
2)
Apelin
Bombesin
- BRS3
- GRPR
- NMBR)
- Bradykinin (B1
- B2)
Chemokine
Cholecystokinin (A
B)
Endothelin
- A
- B
Formyl peptide (1
2
3)
FSH
Galanin (1
2
3)
Gonadotropin-releasing hormone (1
2)
Ghrelin
Kisspeptin
Luteinizing hormone/choriogonadotropin
MAS (1
1L
D
E
F
G
X1
X2
X3
X4)
Melanocortin (1
2
3
4
5)
MCHR (1
2)
Motilin
Opioid (Delta
Kappa
Mu
Nociceptin & Zeta, but not Sigma)
Orexin (1
2)
Oxytocin
Prokineticin (1
2)
Prolactin-releasing peptide
Relaxin (1
2
3
4)
Somatostatin (1
2
3
4
5)
Tachykinin (1
2
3)
Thyrotropin
Thyrotropin-releasing hormone
Urotensin-II
Vasopressin (1A
1B
2)

Miscellaneous

Taste, bitter	TAS2R 1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor type 1
Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)
Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin-like

Adhesion	ADGRB Brain-specific angiogenesis inhibitor 1 2 3 ADGRC Cadherin 1 2 3 ADGRE EMR 1 2 3 CD97 ADGRG 1 2 3 4 5 6 7 ADGRL Latrophilin 1 2 3 ELTD1
Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)
Other	Calcitonin CALCRL Corticotropin-releasing hormone (1 2) Glucagon (GR GIPR GLP1R GLP2R) Growth-hormone-releasing hormone PACAPR1 GPR Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste, sweet	TAS1R 1 2 3 Vomeronasal receptor, type 2
Other	Calcium-sensing receptor GABA_B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled & Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)
Smoothened	Smoothened

Neuropeptide receptors

G protein-coupled receptor

Hormone receptors

Hypothalamic	CRH FSH LHRH TRH Somatostatin
Pituitary	Vasopressin 1A 1B 2 Oxytocin LHCG TSH
Other	Atrial natriuretic factor NPR3 Calcitonin Cholecystokinin A B VIP