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To investigate receptor selectivity and possible species selectivity of a number of NPY analogues and fragments, receptor binding studies were performed using cell lines and membranes of several species. NPY displays 4-25-fold higher affinity for the Y 2 receptor than for the Y 1 receptor. The affinity of [Leu 31 ,Pro 34 ]NPY is 7-60-fold higher for the Y...
The relationship between vessel tone and cAMP production induced by vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), peptide histidine valine (PHV), pituitary adenylate cyclase activating polypeptide (PACAP-27 and PACAP-38), and neuropeptide Y (NPY) was investigated in rabbit ovarian arteries in vitro. VIP, PHM, PHV, PACAP-27, and PACAP-38 added in single-dose experiments...
Balasubramaniam, A. Neuropeptide Y family of hormones: Receptor subtypes and antagonists. Peptides 18(3) 445–457, 1997.—Neuropeptide Y (NPY) is the most abundant peptide present in the mammalian central and peripheral nervous system. NPY exhibits a variety of potent central and peripheral effects including those on feeding, memory, blood pressure, cardiac contractility and intestinal secretions. Classical...
We cloned and expressed the rat Y4 receptor for pancreatic polypeptide (PP). Structure-activity profiles derived from 125 I-PP binding assays and [cAMP] radioimmunoassays reveal a selective receptor interaction with rat PP vs. neuropeptide Y (NPY) or peptide YY (PYY). Rat and human Y4 receptor clones share 75% amino acid identity. Based on [cAMP] radioimmunoassay, the human Y4...
Schober, D. A., A. M. Van Abbema, D. L. Smiley, R. F. Bruns and D. R. Gehlert. The neuropeptide Y Y 1 antagonist, 1229U91, a potent agonist for the human pancreatic polypeptide-preferring (NPY Y 4 ) receptor. Peptides 19(3) 537-542, 1998.-Recently, a novel high-affinity peptide antagonist, 1229U91, was published as a selective neuropeptide Y Y 1 antagonist. The selectivity...
We have cloned the guinea pig neuropeptide Y (NPY) Y 1 receptor and found it to be 92-93% identical to other cloned mammalian Y 1 receptors. Porcine NPY and peptide YY (PYY) displayed affinities of 43 pM and 48 pM, respectively. NPY2-36 and NPY3-36 had 6- and 46-fold lower affinity, respectively, than intact NPY. Functional coupling was measured by using a microphysiometer. Human NPY...
α-Melanocyte-stimulating hormone (α-MSH) appears to play a tonic inhibitory role in feeding and energy storage. MTII, a specific synthetic MC3-R/MC4-R agonist, has similar effects on feeding in rats. The current studies demonstrate that PVN administration of α-MSH or MTII decreases nocturnal and NPY-stimulated food intake without causing aversive effects. Co-administration with NPY of 600 pmol α-MSH...
The neuropeptide Y-family receptor Y4 differs extensively between human and rat in sequence, receptor binding, and anatomical distribution. We have investigated the differences in binding profile between the cloned human, rat, and guinea pig Y4 receptors using NPY analogues with single amino acid replacements or deletion of the central portion. The most striking result was the increase in affinity...
Neuropeptide Y (NPY) and pancreatic polypeptide (PP) bind to the Y-receptors with very different affinities: NPY has high affinity for the receptors Y 1 , Y 2 and Y 5 , while PP binds only to Y 4 -receptor with picomolar affinity. By exchanging of specific amino acid positions between the two peptides, we developed 38 full-length PP/NPY chimeras with binding properties...
Endothelin-1 (ET-1) undergoes an about 8-h (circaoctohoran) rather than a circadian variation in clinical health. Herein, 24h plasma concentrations of vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NpY), and cortisol used as reference, were obtained from 20 healthy young adults starting at 07:00 or 19:00h. Like ET-1, SP and NpY undergo a circaoctohoran variation, whereas VIP...
The melanocortin signaling system is orchestrated by two, independent groups of neurons in the hypothalamic arcuate nucleus with opposing functions that synthesize either alpha-melanocyte stimulating hormone (α-MSH) or agouti-related protein (AGRP). These neurons exert regulatory control over hypophysiotropic TRH neurons in the hypothalamic paraventricular nucleus (PVN) at least in part through direct,...
We studied the effects of neuropeptide Y (NPY) and NPY-related receptor specific peptides on functions of carrageenan-elicited granulocytes in vitro and ability of NPY to modulate carrageenan-induced air pouch inflammation in rats in vivo. Anti-inflammatory effect of NPY comprises reduced granulocyte accumulation into the air pouch, to some extent attenuation of phagocytosis, attained via Y1 receptor,...
Although it is broadly accepted that the immune system and the nervous system functionally interact with each other at various levels, many aspects of this crosstalk still remain unclear. One player in this interaction is neuropeptide Y (NPY), a sympathetic neurotransmitter, which has been demonstrated to regulate a broad variety of immune functions. In this review we will outline key findings on...
Activation of the hypothalamic-pituitary–adrenal gland (HPA) axis can modulate the immune system. Cytokines and neuropeptide Y (NPY) are potent regulators of the HPA axis and are both produced by the adrenal medulla. The cytokine interleukin-1β (IL-1β) belongs to the interleukin-1 family along with interleukin-1α and the interleukin receptor antagonist (IL-1ra). The aim of the present study was to...
Growing evidence suggests that endocardial endothelial cells (EECs) may play an important role in the regulation of cardiac function by releasing several cardioactive factors such as endothelin-1 (ET-1), Angiotensin II (Ang II) and nitric oxide (NO). In our laboratory, we demonstrated that similar to ET-1, EECs do possess different types of NPY receptors, specifically Y 1 and Y 2 receptors...
The abundantly expressed neuropeptide Y (NPY) has potent effects on feeding, body weight, and blood pressure, and exhibits important functions in various behavioral domains such as motor activity and anxiety. The potent neurotransmitter exerts its biological effects through at least five G-protein coupled receptors termed Y 1 , Y 2 , Y 4 , Y 5 , and y 6 . The...
Seizures induce profound plastic changes in the brain, including altered expression of neuropeptide Y (NPY) and its receptors. Here, I discuss a potential role of NPY plasticity in the developmental brain: in a rat model of febrile seizures (FS), the most common type of seizures in infants and young children, NPY expression was up-regulated in hippocampus after experimentally induced FS. Interestingly,...
Neuropeptide Y (NPY)-induced modulation of the immune and inflammatory responses is regulated by tissue-specific expression of different receptor subtypes (Y1–Y6) and the activity of the enzyme dipeptidyl peptidase 4 (DP4, CD26) which terminates the action of NPY on Y1 receptor subtype. The present study investigated the age-dependent effect of NPY on inflammatory paw edema and macrophage nitric oxide...
Elucidating how neuropeptides affect physiology may result in delineating peptidergic mechanisms and identifying antagonists for application in basic and translational science. Human neuropeptide Y (NPY) regulates cardiac activity; frequently invertebrates contain orthologs of vertebrate peptides. We report invertebrate NPY-like neuropeptide F (NPF) arrested the signal frequency of the slow phase...
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