ICV NPY Y1 receptor agonist but not Y5 agonist induces torpor-like hypothermia in cold-acclimated Siberian hamsters

2007 ◽  
Vol 292 (6) ◽  
pp. R2299-R2311 ◽  
Author(s):  
Kimberly M. Pelz ◽  
John Dark
Keyword(s):  
Receptor Activation ◽  
Neural Mechanisms ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Y1 Receptor ◽  
Siberian Hamsters ◽  
Npy Receptor ◽  
Intracerebroventricular Injections ◽  
Metabolic Expenditure ◽  
Compare And Contrast

The reduced metabolism derived from daily torpor enables numerous small mammals, including Siberian hamsters, to survive periods of energetic challenge. Little is known of the neural mechanisms underlying the initiation and expression of torpor. Hypothalamic neuropeptide Y (NPY) contributes to surviving energetic challenges by both increasing food ingestion and reducing metabolic expenditure. Intracerebroventricular injections of NPY in cold-acclimated Siberian hamsters induce torpor-like hypothermia comparable to natural torpor. Multiple NPY receptor subtypes have been identified, and the Y1 receptor and Y5 receptor both contribute to the orexigenic effect of NPY. The purpose of this research was to compare and contrast the effects of Y1 receptor activation by a specific Y1 agonist ([d-Arg25]-NPY) or Y5 receptor activation by a specific Y5 agonist ([d-Trp34]-NPY) on body temperature and subsequent food intake in cold-acclimated Siberian hamsters. Intracerebroventricular injections of Y1 agonist produced torporlike hypothermia closely resembling that induced by intracerebroventricular NPY. The intracerebroventricular Y5 agonist infrequently produced hypothermia reaching criterion for torpor and that failed to resemble either NPY-induced or natural torpor. Combined injections of Y1 and Y5 agonists resulted in hypothermia comparable to Y5 agonist treatments alone, negating the mimicry of NPY treatment seen with Y1 agonist alone. Prior treatment with Y1 agonist or Y5 agonist surprisingly had lingering effects on NPY-induced torpor expression, Y1 agonist enhanced and Y5 agonist inhibited the effect of NPY. The ability of NPY to induce torporlike hypothermia, especially its initiation, most likely involves activation of the NPY Y1 receptor subtype.

scholarly journals Selective activation of central NPY Y1 vs. Y5 receptor elicits hyperinsulinemia via distinct mechanisms

2004 ◽  
Vol 287 (4) ◽  
pp. E706-E711 ◽  
Author(s):  
Jun Gao ◽  
Lorraine Ghibaudi ◽  
Joyce J. Hwa
Keyword(s):  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Central Administration ◽  
Food Ingestion ◽  
Selective Activation ◽  
Glucose Levels ◽  
Y1 Receptor ◽  
Npy Receptor ◽  
Plasma Insulin Levels ◽  
Long Evans

Central administration of neuropeptide Y (NPY) stimulates hyperphagia and hyperinsulinemia. Recent evidence has suggested that the Y1 and Y5 receptor subtypes may both mediate NPY-stimulated feeding. The present study attempts to further characterize the role of central NPY receptor subtypes involved in hyperinsulinemia. NPY and peptide analogs of NPY that selectively activated the NPY Y1 or Y5 receptor subtype induced feeding and hyperinsulinemia in satiated Long Evans rats, whereas NPY analogs that selectively activated the NPY Y2 or Y4 receptor subtype did not. To determine whether NPY-induced hyperinsulinemia is secondary to its hyperphagic effect, we compared the plasma insulin levels in the presence and absence of food after a 1-min central infusion of NPY and its analogs at 15, 60, and 120 min postinfusion. Our data suggest that selective activation of central NPY Y1 receptor subtype induced hyperinsulinemia independent of food ingestion, whereas the NPY Y5 receptor-induced hyperinsulinemia was dependent on food ingestion. Central administration of the selective Y1 receptor agonist d-Arg25 NPY eventually decreased plasma glucose levels 2 h postinfusion in Long Evans rats.

NPY Y1 receptor antagonist prevents NPY-induced torporlike hypothermia in cold-acclimated Siberian hamsters

2008 ◽  
Vol 294 (1) ◽  
pp. R236-R245 ◽  
Author(s):  
John Dark ◽  
Kimberly M. Pelz
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Phodopus Sungorus ◽  
Food Ingestion ◽  
Research Groups ◽  
Ambient Temperatures ◽  
Y1 Receptor ◽  
Siberian Hamsters ◽  
Intracerebroventricular Injections

Siberian hamsters ( Phodopus sungorus) undergo bouts of daily torpor during which body temperature decreases by as much as 20°C and provides a significant savings in energy expenditure. Natural torpor in this species is normally triggered by winterlike photoperiods and low ambient temperatures. Intracerebroventricular injection of neuropeptide Y (NPY) reliably induces torporlike hypothermia that resembles natural torpor. NPY-induced torporlike hypothermia is also produced by intracerebroventricular injections of an NPY Y1 receptor agonist but not by injections of an NPY Y5 receptor agonist. In this research, groups of cold-acclimated Siberian hamsters were either coinjected with a Y1 receptor antagonist (1229U91) and NPY or were coinjected with a Y5 receptor antagonist ( CGP71683 ) and NPY in counterbalanced designs. Paired vehicle + NPY induced torporlike hypothermia in 92% of the hamsters, whereas coinjection of Y1 antagonist + NPY induced torporlike hypothermia in 4% of the hamsters. In contrast, paired injections of vehicle + NPY and Y5 antagonist + NPY induced torporlike hypothermia in 100% and 91% of the hamsters, respectively. Although Y5 antagonist treatment alone had no effect on body temperature, Y1 antagonist injections produced hyperthermia compared with controls. Both Y1 antagonist and Y5 antagonist injections significantly reduced food ingestion 24 h after treatment. We conclude that activation of NPY 1 receptors is both sufficient and necessary for NPY-induced torporlike hypothermia.

scholarly journals Effect of the Gintonin-Enriched Fraction on Glucagon-Like-Protein-1 Release

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6298
Author(s):  
Rami Lee ◽  
Sun-Hye Choi ◽  
Han-Sung Cho ◽  
Hongik Hwang ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Western Blotting ◽  
Receptor Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Receptor Ligands ◽  
Lpa Receptor ◽  
Beneficial Effects

Ginseng-derived gintonin reportedly contains functional lysophosphatidic acids (LPAs) as LPA receptor ligands. The effect of the gintonin-enriched fraction (GEF) on in vitro and in vivo glucagon-like protein-1 (GLP-1) secretion, which is known to stimulate insulin secretion, via LPA receptor(s) remains unclear. Accordingly, we examined the effects of GEF on GLP-1 secretion using human enteroendocrine NCI-H716 cells. The expression of several of LPA receptor subtypes in NCI-H716 cells using qPCR and Western blotting was examined. LPA receptor subtype expression was in the following order: LPA6 > LPA2 > LPA4 > LPA5 > LPA1 (qPCR), and LPA6 > LPA4 > LPA2 > LPA1 > LPA3 > LPA5 (Western blotting). GEF-stimulated GLP-1 secretion occurred in a dose- and time-dependent manner, which was suppressed by cAMP-Rp, a cAMP antagonist, but not by U73122, a phospholipase C inhibitor. Furthermore, silencing the human LPA6 receptor attenuated GEF-mediated GLP-1 secretion. In mice, low-dose GEF (50 mg/kg, peroral) increased serum GLP-1 levels; this effect was not blocked by Ki16425 co-treatment. Our findings indicate that GEF-induced GLP-1 secretion could be achieved via LPA6 receptor activation through the cAMP pathway. Hence, GEF-induced GLP secretion via LPA6 receptor regulation might be responsible for its beneficial effects on human endocrine physiology.

scholarly journals Selective Regulation of Somatostatin Receptor Subtype Signaling: Evidence for Constitutive Receptor Activation

2007 ◽  
Vol 21 (10) ◽  
pp. 2565-2578 ◽  
Author(s):  
Anat Ben-Shlomo ◽  
Oxana Pichurin ◽  
Nicole J. Barshop ◽  
Kolja A. Wawrowsky ◽  
John Taylor ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Receptor Activation ◽  
Receptor Subtype ◽  
Pituitary Hormone ◽  
Receptor Subtypes ◽  
Camp Accumulation ◽  
Acth Secretion ◽  
Somatostatin Receptor Subtypes

Abstract Anterior pituitary hormone secretion is under tonic suppression by hypothalamic somatostatin signaling through somatostatin receptor subtypes (SSTs). Because some hormonal axes are known to be abnormally regulated by ligand-independent constitutively active G protein-coupled receptors, we tested pituitary SSTs for selective constitutive signaling. We therefore differentially silenced endogenous SST2, SST3, and SST5 in somatostatin-sensitive ACTH-secreting mouse AtT-20 pituitary corticotroph cells using small inhibitory RNA (siRNA) and analyzed downstream SSTs-regulated pathways. Transfection with siRNA reduced specific receptor subtype mRNA expression up to 82%. Specificity of receptor silencing was validated against negative controls with different gene-selective siRNAs, concordance of mRNA and cAMP changes, reduced potency of receptor-selective agonists, and phenotype rescue by overexpression of the silenced receptor. Mouse SST3 > SST5 > SST2 knockdown increased basal cAMP accumulation (up to 200%) and ACTH secretion (up to 60%). SST2- and SST5-selective agonist potencies were reduced by SST3- and SST5-silencing, respectively. SST5 > SST2 = SST3 silencing also increased basal levels of ERK1/2 phosphorylation. SST3- and SST5-knockdown increased cAMP was only partially blocked by pertussis toxin. The results show that SST2, SST3, and SST5 exhibit constitutive activity in mouse pituitary corticotroph cells, restraining adenylate cyclase and MAPK activation and ACTH secretion. SST3 mainly inhibits cAMP accumulation and ACTH secretion, whereas SST5 predominantly suppresses MAPK pathway activation. Therefore, SST receptor subtypes control pituitary cell function not only through somatostatin binding to variably expressed cell membrane receptor subtypes, but also by differential ligand-independent receptor-selective constitutive action.

scholarly journals 5-HT2A receptor activation is necessary for CO2-induced arousal

2015 ◽  
Vol 114 (1) ◽  
pp. 233-243 ◽  
Author(s):  
Gordon F. Buchanan ◽  
Haleigh R. Smith ◽  
Amanda MacAskill ◽  
George B. Richerson
Keyword(s):  
Sudden Infant Death ◽  
Receptor Activation ◽  
Sudden Infant ◽  
Protective Mechanism ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Unexpected Death ◽  
Obstructive Sleep ◽  
Embryonic Life

Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive sleep apnea and sudden unexpected death in epilepsy. Serotonin (5-HT) plays a significant role in hypercapnia-induced arousal. The mechanism of 5-HT's role in this protective response is unknown. Here we sought to identify the specific 5-HT receptor subtype(s) involved in this response. Wild-type mice were pretreated with antagonists against 5-HT receptor subtypes, as well as antagonists against adrenergic, cholinergic, histaminergic, dopaminergic, and orexinergic receptors before challenge with inspired CO2 or hypoxia. Antagonists of 5-HT2A receptors dose-dependently blocked CO2-induced arousal. The 5-HT2C receptor antagonist, RS-102221, and the 5-HT1A receptor agonist, 8-OH-DPAT, attenuated but did not completely block CO2-induced arousal. Blockade of non-5-HT receptors did not affect CO2-induced arousal. None of these drugs had any effect on hypoxia-induced arousal. 5-HT2 receptor agonists were given to mice in which 5-HT neurons had been genetically eliminated during embryonic life ( Lmx1b f/f/p) and which are known to lack CO2-induced arousal. Application of agonists to 5-HT2A, but not 5-HT2C, receptors, dose-dependently restored CO2-induced arousal in these mice. These data identify the 5-HT2A receptor as an important mediator of CO2-induced arousal and suggest that, while 5-HT neurons can be independently activated to drive CO2-induced arousal, in the absence of 5-HT neurons and endogenous 5-HT, 5-HT receptor activation can act in a permissive fashion to facilitate CO2-induced arousal via another as yet unidentified chemosensor system.

scholarly journals Modulatory Action by the Serotonergic System: Behavior and Neurophysiology inDrosophila melanogaster

2016 ◽  
Vol 2016 ◽  
pp. 1-23 ◽  
Author(s):  
Zana R. Majeed ◽  
Esraa Abdeljaber ◽  
Robin Soveland ◽  
Kristin Cornwell ◽  
Aubrey Bankemper ◽  
...  
Keyword(s):  
Motor Activity ◽  
Tryptophan Hydroxylase ◽  
Neural Circuit ◽  
Receptor Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Feeding Behaviors ◽  
Pharmacological Agents ◽  
Motor Circuits ◽  
Sensory Motor

Serotonin modulates various physiological processes and behaviors. This study investigates the role of 5-HT in locomotion and feeding behaviors as well as in modulation of sensory-motor circuits. The 5-HT biosynthesis was dysregulated by feedingDrosophilalarvae 5-HT, a 5-HT precursor, or an inhibitor of tryptophan hydroxylase during early stages of development. The effects of feeding fluoxetine, a selective serotonin reuptake inhibitor, during early second instars were also examined. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or enhanced in both larvae and adult flies. The results demonstrate that disruption of components within the 5-HT system significantly impairs locomotion and feeding behaviors in larvae. Acute activation of 5-HT neurons disrupts normal locomotion activity in adult flies. To determine which 5-HT receptor subtype modulates the evoked sensory-motor activity, pharmacological agents were used. In addition, the activity of 5-HT neurons was enhanced by expressing and activating TrpA1 channels or channelrhodopsin-2 while recording the evoked excitatory postsynaptic potentials (EPSPs) in muscle fibers. 5-HT2 receptor activation mediates a modulatory role in a sensory-motor circuit, and the activation of 5-HT neurons can suppress the neural circuit activity, while fluoxetine can significantly decrease the sensory-motor activity.

scholarly journals NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake

2007 ◽  
Vol 292 (4) ◽  
pp. R1728-R1737 ◽  
Author(s):  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Free Food ◽  
Receptor Activation ◽  
Food Delivery ◽  
Behavioral Changes ◽  
Running Wheel ◽  
Food Hoarding ◽  
Y1 Receptor ◽  
Siberian Hamsters

Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.

Neuropeptide Y binding and inhibition of cAMP accumulation in human neuroepithelioma cells

1990 ◽  
Vol 258 (5) ◽  
pp. C913-C922 ◽  
Author(s):  
L. A. Lobaugh ◽  
P. J. Blackshear
Keyword(s):  
Neuropeptide Y ◽  
Receptor Activation ◽  
Guanine Nucleotides ◽  
Hill Coefficient ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Intact Cells ◽  
Equilibrium Binding ◽  
Npy Receptor

The specific binding of 125I-labeled neuropeptide Y (NPY) and the biological response to NPY receptor activation were measured in cultured human neuroepithelioma (SK-N-MC) cells. A single class of high-affinity binding sites [dissociation constant (KD) = 0.2 nM] was characterized both by equilibrium binding of 125I-NPY concentrations less than 1 nM and kinetically by the initial rates of 125I-NPY association and dissociation. Specific 125I-NPY binding was decreased in a concentration-dependent manner by inclusion of guanine nucleotides in the incubation medium. The existence of multiple affinity states or NPY receptor subtypes was suggested by 1) a Hill coefficient of less than 1.0 obtained when analyzing equilibrium binding with 125I-NPY concentrations greater than 1 nM, 2) biphasic dissociation of 125I-NPY, 3) an increase in the component of rapid dissociation and decrease in the component of slow dissociation when guanine nucleotides were present during dissociation of 125I-NPY, and 4) displacement of 125I-NPY by unlabeled peptide with a slope factor of 0.6. Exposure of intact cells to NPY caused a concentration-dependent pertussis toxin-sensitive inhibition of forskolin-stimulated cellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation [50% effective concentration (EC50) = 0.4 nM]. In contrast, NPY had no effect on cellular inositol phosphate content or protein kinase C activation. These results demonstrate that NPY binds specifically to a G protein-linked receptor that inhibits adenylate cyclase in SK-N-MC cells.

Effects of angiotensin II and nonpeptide receptor antagonists on transduction pathways in rat proximal tubule

1992 ◽  
Vol 263 (4) ◽  
pp. C750-C758 ◽  
Author(s):  
J. Poggioli ◽  
G. Lazar ◽  
P. Houillier ◽  
J. P. Gardin ◽  
J. M. Achard ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Inositol Phosphates ◽  
Inositol Trisphosphate ◽  
Receptor Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
At1 Antagonist ◽  
Rat Proximal Tubule

Because the presence of the angiotensin II (ANG II)-dependent phosphoinositide hydrolysis has been questioned from studies in proximal cells in culture, we looked for this transduction pathway in suspension of freshly isolated rat proximal tubule fragments. ANG II-receptor activation induced a prompt (within 15 s) and sustained increase in [3H]inositol phosphates (IPs; inositol trisphosphate, inositol bisphosphate, and inositol monophosphate). In fura-2-loaded tubules, it elicited a rapid and biphasic rise in cytosolic free calcium ([Ca2+]i) with an early peak (within 15 s) followed by a plateau. The peak was maintained in the absence of extracellular calcium. ANG II-induced inositol trisphosphate and [Ca2+]i rises showed a similar dose dependency, with a 50% effective concentration (EC50) of 2.9 and 5.5 nM, respectively. We checked that ANG II inhibited basal (EC50 4.4 nM) and parathyroid hormone- and forskolin-stimulated cAMP production, the latter effect being inhibited by pertussis toxin pretreatment. The effects of ANG II on IPs and [Ca2+]i were inhibited by the ANG II receptor subtype 1 (AT1) antagonist losartan and not by the ANG II receptor subtype 2 (AT2) antagonists PD 123177 and PD 123319. The effect of ANG II on forskolin-stimulated cAMP was inhibited by losartan and not by PD 123319. In agreement with these results, specific binding of 125I-[Sar1,Ile8]ANG II was markedly inhibited by losartan, whereas PD 123319 had no effect. These results demonstrate that AT1 receptor subtypes are present in intact rat proximal tubule cells and are coupled to both IPs-Ca2+ and cAMP signaling pathways. No evidence for AT2 receptor subtype is found.

Regulation of vasopressin secretion by ETA and ETB receptors in compartmentalized rat hypothalamo-neurohypophysial explants

2004 ◽  
Vol 286 (4) ◽  
pp. E535-E541 ◽  
Author(s):  
Noreen F. Rossi
Keyword(s):  
Receptor Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Posterior Pituitary ◽  
Unique Combination ◽  
Vasopressin Secretion ◽  
Hypothalamic Level

The endothelins (ET) have been implicated in vasopressin (AVP) release in vivo and in vitro. The effects of ET in this system are complex, and the net AVP secretory response likely depends on a unique combination of ET isoform, ET receptor subtype, and neural locus. The purpose of these studies was to examine the role of ET receptor subtypes at hypothalamic vs. neurohypophysial sites on somatodendritic and neurohypophysial AVP secretion. Experiments were done in cultured explants of the hypothalamo-neurohypophysial system of Long Evans rats. Either the whole explant (standard) or only the hypothalamus or posterior pituitary (compartmentalized) was exposed to log dose increases (0.01-10 nM) of the agonists ET-1 (ETA selective), ET-3 (nonselective), or IRL-1620 (ETB selective) with or without selective ETA (BQ-123, 2-200 nM) or ETB (IRL-1038, 6-600 nM) receptor antagonism. In standard explants, ET-1 and ET-3 dose-dependently increased, whereas IRL-1620 decreased net AVP release. Hypothalamic ETB receptor activation increased both somatodendritic and neurohypophysial AVP release. At least one intervening synapse was involved, as tetrodotoxin blocked the response. Activation of ETA receptors at the hypothalamic level inhibited, whereas ETA receptor activation at the posterior pituitary stimulated, neurohypophysial AVP secretion. Antagonism of hypothalamic ETA receptors potentiated the stimulatory effect of ET-1 and ET-3 on neurohypophysial secretion, an effect not observed with ETB receptor-induced somatodendritic release of AVP. Thus the response of whole explants reflects the net result of both stimulatory and inhibitory inputs. The integration of these excitatory and inhibitory inputs endows the vasopressinergic system with greater plasticity in its response to physiological and pathophysiological states.

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