Disease relevance of NPY

• We show that insulin secretion in the insulinoma cell line RIN 5AH is inhibited by NPY [1].
• Neuropeptide Y inhibition of insulin secretion is blocked by incubation with pertussis toxin, implying that the effect is via a G-protein (Gi or Go) coupled receptor [1].
• Emesis was sometimes seen following large IV bolus doses of neuropeptide Y (NPY), but none was seen following IV injection of pancreatic polypeptide (PP) [2].
• In dorsal root ganglion S2, Calcitonine Gene-Related Peptide and neuronal Nitric Oxide resulted to be the most frequently present neurotransmitters, followed by Vasoactive Intestinal Peptide, Vesicular Acetylcholine Transporter, Leu-Enkephaline, Substance P, Tyrosine Hydroxylase and Neuropeptide Y [3].
• The Y1 type of binding site, characterized on a human neuroblastoma cell line, MC-IXC, and a rat pheochromocytoma cell line, PC-12, binds NPY with a dissociation constant (Kd) of a few nanomolar but does not bind NPY13-36 [4].

Psychiatry related information on NPY

• NPY promptly increased short-term food intake and observed feeding behaviors at 10.0, 3.3, 1.1, and 0.37 micrograms NPY, but there was no effect on 24 hr food intake [5].
• The effect of neuropeptide Y on the motor activity of the circular and longitudinal muscle of the guinea pig small intestine was investigated [6].

High impact information on NPY

• Neuropeptide Y inhibits excitatory enteric neurons supplying the circular muscle of the guinea pig small intestine [6].
• Further analysis showed that neuropeptide Y did not act directly on intestinal muscle but interrupted excitatory pathways of the enteric nervous system [6].
• Neuropeptide Y also blocked nerve-mediated phasic contractions of the circular muscle, induced by dimethylphenylpiperazinium or ceruletide, and abolished the peristaltic movements of the small intestine [6].
• The neuropeptide Y-containing nerve cell bodies were preferentially located in the submucous ganglia [7].
• These findings provide a morphologic basis for the possibility that neuropeptide Y may act as a transmitter and exert postsynaptic effects on intrinsic neurons, in addition to participating in the regulation of smooth muscle activity and epithelial cell functions [7].

Chemical compound and disease context of NPY

• Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells [1].
• An attempt to determine the consequences of prolonged ischemia on simultaneous regional changes in norepinephrine (NE) and neuropeptide Y (NPY) interstitial myocardial concentrations in a pig model in vivo was made [8].
• These results suggest that NPY increases [Ca2+]i by a pertussis toxin-sensitive GTP binding protein-involved mechanism which is not mediated by the intracellular messengers such as Ins(1,4,5)P3 and cyclic AMP [9].
• Second, pertussis toxin abolished the [Ca2+]i rise induced by NPY, but not by BK or ATII [9].
• No differences in methacholine- or carbachol-induced bradycardia were observed between control and NPY groups in either species [10].

Biological context of NPY

• PYY or NPY did not cause muscle contraction or inhibit muscle contraction induced by carbachol, endothelin-1 or KCl [11].
• In this study, the selectivity of this compound, BIBP 3226, as a functional Y1 receptor antagonist, and the possible role of endogenous NPY in sympathetic vasoconstriction in different vascular beds have been investigated in anaesthetized pigs [12].
• However, BIIE0246 caused splenic vasodilatation per se when given after yohimbine.It is concluded that the renal sympathetic nerves in the pig possess NPY Y(2) receptors, which upon activation inhibit transmitter (noradrenaline and NPY) release [13].
• In this study, we examined the actions of NPY on ion transport in the porcine distal jejunum mucosa-submucosa in vitro [14].
• NPY attenuated increases in Isc produced by electrical stimulation of enteric neurons with an IC50 = 5 nmol/l. The actions of the peptide on basal and cyclic AMP-induced ion transport were abolished by the neuronal conduction blocker tetrodotoxin, but not by the opiate antagonist naloxone [14].

Anatomical context of NPY

• The aim of the present study was to examine which NPY receptors are coupled to inhibition of parasympathetically-mediated contractions of the isolated guinea pig trachea [15].
• In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP [16].
• The NPY antiserum (102B) reacted with nerves in many areas of both the central and peripheral nervous systems, but it did not stain endocrine cells of the pancreas or intestine [17].
• High pressure liquid chromatography analysis revealed that the NPY-immunoreactive material from cerebral cortex and vas deferens had elution profiles similar to those of standard porcine NPY [17].
• Inhibition of insulin secretion in this cell line by NPY fragments and analogues also shows a Y1 receptor-like profile [1].

Associations of NPY with chemical compounds

• Pretreatment with the Y1 receptor-selective antagonist BIBP3226 (1 microM) failed to prevent the NPY-induced inhibition [15].
• PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion [16].
• Furthermore, NPY via Y1 receptor mechanisms seems to be of major importance for the long-lasting component of the reserpine resistant sympathetic vasoconstriction in many vascular beds, and for the maximal vasoconstrictor response in the kidney [12].
• NPY 26-36 was without effect as were C-terminal carboxy-deaminated NPY and glycine extended NPY (NPY-Gly-Lys-Arg) [18].
• The alpha-adrenoceptor blocker phentolamine diminished the effects of NPY on basal, but not cyclic AMP-induced Isc [14].

Physical interactions of NPY

• PYY and NPY interact with Y2 receptors to inhibit this CCK-induced muscle contraction by an effect not related to NO [11].

Regulatory relationships of NPY

• We therefore infused synthetic porcine NPY directly into the pancreatic artery in anaesthetized pigs to study its direct in vivo influence on pancreatic blood flow and on insulin and glucagon secretion [19].

Other interactions of NPY

• The relative potencies for inhibiting [125I]PYY binding were PYY > or = NPY > NPY(13-36) [20].
• In paravertebral ganglion S1, Tyrosine Hydroxylase and Neuropeptide Y were the most frequently present substances [3].
• Endogenous neuropeptide Y acting on the neuropeptide Y Y1 receptor is likely to account for the long-lasting component of the reserpine-resistant sympathetic vasoconstriction upon high frequency stimulation in hind limb and nasal mucosa [21].
• GluDCase was co-localized with CCK, SRIF, or NPY not only in cell somata, but also in small punctate structures, which are likely to be axon terminals [22].
• Topography of NPY-, somatostatin-, and VIP-immunoreactive, neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion and their projection to the pylorus [23].

Analytical, diagnostic and therapeutic context of NPY

• This was also seen even if no detectable cross-reactivity with NPY was found in radioimmunoassay [17].
• Northern blot analysis using a Y1-receptor specific probe shows that NPY Y1 receptors are expressed by RIN 5AH cells [1].
• Reperfusion after 2 h of renal ischaemia was associated with local overflow of noradrenaline (NA) but not of NPY-like immunoreactivity (-LI) [24].
• Here we investigate the effect of NPY in intracellular Ca2+ release, using isolated rat cardiac myocytes and confocal microscopy [25].
• Characterization and molecular cloning of vascular neuropeptide Y receptor subtypes in pig and dog [26].

References