Biomaterial Database

The neuropeptide Y Y1 antagonist, 1229U91, a potent agonist for the human pancreatic polypeptide-preferring (NPY Y4) receptor. 1998

D A Schober, and A M Van Abbema, and D L Smiley, and R F Bruns, and D R Gehlert

Lilly Neuroscience Research, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.

Recently, a novel high-affinity peptide antagonist, 1229U91, was published as a selective neuropeptide Y Y1 antagonist. The selectivity of 1229U91 was evaluated in the human NPY Y1 receptor containing cell line, SK-N-MC, and cells containing the cloned human NPY Y2, the pancreatic polypeptide-preferring (NPY Y4), and the NPY Y5 receptors. 1229U91 potently displaced [125I]-peptide YY (PYY) binding to human NPY Y1 receptors (IC50 = 0.245+/-0.004 nM, n = 4). but displayed little affinity for the human NPY Y2 and Y5 receptors (IC50 > 1000 nM). Interestingly, 1229U91 displaced [125I]-PYY with even greater affinity at the human NPY Y4 receptor (IC50 = 0.081+/-0.009 nM, n = 4). Using a cyclic AMP accumulation assay, 1229U91 blocked NPY inhibition of forskolin-induced adenylate cyclase activity in NPY Y1 receptor containing SK-N-MC cells. In the human NPY Y4 receptor expressing cell line, 1229U91 did not block pancreatic polypeptide (PP) inhibition of forskolin stimulated adenylate cyclase. However, in the absence of PP, 1229U91 was able to inhibit forskolin stimulated cyclic AMP accumulation (IC50 = 7.16+/-2.8 nM, n = 4). We conclude that 1229U91 binds non-selectively with high affinity to both human NPY Y1 and Y4 receptors. Furthermore, 1229U91 displays antagonist activity at the NPY Y1 receptor, while having agonist activity at the NPY Y4 receptor.

UI	MeSH Term	Description	Entries
D010456	Peptides, Cyclic	Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).	Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001120	Arginine	An essential amino acid that is physiologically active in the L-form.	Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D016466	CHO Cells	CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.	CHO Cell,Cell, CHO,Cells, CHO
D017476	Receptors, Neuropeptide Y	Cell surface proteins that bind neuropeptide Y with high affinity and trigger intracellular changes which influence the behavior of cells.	Neuropeptide Y Receptors,Neuropeptide Y Receptor,Receptor, Neuropeptide Y