[Leu31,Pro34]-Neuropeptide Y (human, rat)

Evidence for involvement of neuropeptide Y receptors in the regulation of food intake: studies with Y1-selective antagonist BIBP3226.[Pubmed:9723965]

Br J Pharmacol. 1998 Aug;124(7):1507-15.

1. Experiments were conducted to evaluate the effects of the novel non-peptide neuropeptide Y Y1 receptor antagonist, BIBP3226 (N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine amide) on spontaneous, fasting-induced and NPY-induced food intake in rats. In addition to consumption of regular chow, the effects of BIBP3226 on consumption of highly palatable sweetened mash were monitored in a 1 h test on first exposure and after familiarization with novel food. 2. BIBP3226 (10.0 nmol, i.c.v.) had no effect on the consumption of regular chow, but reduced significantly the intake of highly palatable diet and the food intake stimulated by fasting (24 h). Neuropeptide Y (NPY, 1.0 nmol, i.c.v.) significantly increased the consumption of regular rat chow. This orexigenic effect of NPY was blocked by BIBP3226 (10.0 nmol, administered i.c.v. 5 min before NPY) at 30 min and 4 h, but not at 1 and 2 h. When animals were pretreated with diazepam (0.5 mg kg(-1), i.p., 20 min before NPY), BIBP3226 failed to suppress NPY-induced feeding. 3. An NPY Y1 and Y3 receptor agonist, [Leu31,Pro34]NPY and a Y5 receptor agonist human peptide YY3-36 (hPYY3-36, both 30 pmol), microinjected into the paraventricular nucleus of the hypothalamus (PVN) increased the consumption of regular rat chow. BIBP3226 (0.4 nmol, into the PVN) completely blocked the stimulatory effect of [Leu31,Pro34]NPY but not that of hPYY3-36. BIBP3226 (0.4 nmol) alone failed to modify the consumption of the regular chow. Higher doses of BIBP3226 (1.0 and 2.0 nmol) injected into the vicinity of the PVN reduced the consumption of the sweetened mash. 4. These results suggest that both the NPY Y1 and Y5 receptors in the PVN are involved in the regulation of food intake. The stimulatory effect of exogenous NPY is probably mediated through an NPY receptor subtype that is not identical with the Y1 receptor (possibly Y5 receptor). However, the NPY Y1 receptors may mediate the effect of endogenous NPY in conditions of increased energy demand or on intake of highly palatable diets.

Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.[Pubmed:7592911]

J Biol Chem. 1995 Nov 10;270(45):26762-5.

The pancreatic polypeptide family includes pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY). Members of the PP family regulate numerous physiological processes, including appetite, gastrointestinal transit, anxiety, and blood pressure. Of the multiple Y-type receptors proposed for PP family members, only the Y1 subtype has been cloned previously. We now report the cloning of an additional Y-type receptor, designated Y4, by homology screening of a human placental genomic library with transmembrane (TM) probes derived from the rat Y1 gene. The Y4 genomic clone encodes a predicted protein of 375 amino acids that is most homologous to Y1 receptors from human, rat, and mouse (42% overall; 55% in TM). 125I-PYY binding to transiently expressed Y4 receptors was saturable (pKd = 9.89) and displaceable by human PP family derivatives: PP (pKi = 10.25) approximately PP2-36 (pKi = 10.06) > PYY (pKi = 9.06) approximately [Leu31,Pro34]NPY (pKi = 8.95) > NPY (pKi = 8.68) > PP13-36 (pKi = 7.13) > PP31-36 (pKi = 6.46) > PP31-36 free acid (pKi < 5). Human PP decreased [cAMP] and increased intracellular [Ca2+] in Y4-transfected LMTK- cells. Y4 mRNA was detected by reverse transcriptase-polymerase chain reaction in human brain, coronary artery, and ileum, suggesting potential roles for Y4 receptors in central nervous system, cardiovascular, and gastrointestinal function.

[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist.[Pubmed:2153286]

Proc Natl Acad Sci U S A. 1990 Jan;87(1):182-6.

Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31, Pro34]NPY is also active in vivo as it is even more potent than NPY in increasing blood pressure in anesthetized rats. It is concluded that [Leu31, Pro34]NPY is a specific Y1 receptor agonist and that the analog or variants of it can be useful in delineating the physiological importance of Y1 receptors.