Biomedical subjects

E S Corp

Publications and source records attributed to E S Corp.

At least 19 recordsLinked to original sources

PubMed2001

Feeding after fourth ventricular administration of neuropeptide Y receptor agonists in rats.

Neuropeptide Y (NPY) and peptide YY (PYY) stimulate food intake after injection into the fourth cerebral ventricle, suggesting that NPY receptors in the hindbrain are targets for the stimulatory effect of these peptides on food intake. However, the NPY/PYY receptor subtype mediating the feeding response in the hindbrain is not known. To approach to this question we compared dose-effect of several NPY receptor agonists to stimulate food intake in freely-feeding rats 60- and 120-min after injection into the fourth cerebral ventricle. At the 120-min time point, PYY was 2- to 10-times as potent as NPY over the dose-response range and stimulated twice the total intake at the maximally effective dose (2-fold greater efficacy). NPY was 2-times as potent as the Y1, Y5 receptor agonist, [Leu(31)Pro(34)]NPY but acted with comparable efficacy. The Y5-, Y2-differentiating receptor agonist, NPY 2-36, was comparable in potency to PYY at low doses but equal in efficacy NPY and [Leu(31)Pro(34)]NPY. The Y2 receptor agonist, NPY 13-36, produced only a marginal effect on total food intake. The profile of agonist potency after fourth cerebral ventricle administration is similar to the profile obtained when these or related agonists are injected in the region of the hypothalamus. Agonists at both Y1 and Y5 receptors stimulated food intake with a rank order of potency that does not conclusively favor the exclusive involvement of a single known NPY receptor subtype. Thus it is possible that the ingestive effects of NPY and PYY are mediated by multiple or novel receptor subtypes in the hindbrain. And the relatively greater potency and efficacy of PYY raises the possibility that a novel PYY-preferring receptor in the hindbrain is involved in the stimulation of food intake.

Animals↗

PubMed2001

Effects of naltrexone and CCK on estrous behavior and food intake in Syrian hamsters.

Food deprivation inhibits estrous behavior in several species of rodents, but little is known about the neurotransmitter systems mediating this phenomenon. We determined whether partial blockade of opioid receptors by continuous infusion of naltrexone and/or acute peripheral injection of cholecystokinin (CCK) administration would overcome the suppressive effects of food deprivation on estrous behavior in Syrian hamsters. Contrary to expectation, naltrexone produced a slight suppression of estrous behavior, and systemic CCK administration had no effect. This dose of naltrexone was sufficient to reduce in vivo binding of [(3)H]naloxone in the brain, and both compounds affected other parameters such as food intake and body weight gain. Thus, the doses of CCK and naltrexone that were used were physiologically effective. These findings suggest that neither peripheral CCK nor opioid systems are likely to play a major role in the suppression of hamster estrous behavior by food deprivation.

Animals↗

PubMed2001

Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters.

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3-36) and [Leu(31),Pro(34)]PYY, on lordosis duration and food intake. PYY-(3-36) produced a 91% reduction in lordosis duration at 0.24 nmol. [Leu(31),Pro(34)]PYY was less potent, producing a reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3-36) and [Leu(31),Pro(34)]PYY stimulated comparable dose-related increases in total food intake (2 h), suggesting Y5 receptors are involved in feeding. The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3-36) or [Leu(31),Pro(34)]PYY at a dose of each that differentiated between the two behaviors. Some differences were seen in the distribution of Fos-IR produced by the two peptides. Overall, however, the patterns of expression were similar. Our behavioral and anatomic results suggest that NPY-containing pathways controlling estrous and feeding behavior innervate similar nuclei, with the divergence in pathways controlling the separate behaviors characterized by linkage to different NPY receptor subtypes.

Analysis of Variance↗

PubMed1998

Intracerebroventricular glucagon-like peptide-1 (7-36) amide inhibits sham feeding in rats without eliciting satiety.

Glucagonlike peptide-1 (7-36) amide (GLP-1) and its receptors are present in several brain regions and may play a role in the physiological control of feeding. To investigate the effect of GLP-1 on eating in the absence of postingestive food stimuli, rats were implanted with gastric cannulas for sham feeding and lateral ventricular cannulas for infusion of GLP-1. Rats (n = 10) sham fed 0.8 mol/L sucrose for 45 min, beginning 5 min after intracerebroventricular (icv) infusion of 2.5 microL of artificial cerebrospinal fluid with 0-30 microg of GLP-1 . Behaviors were observed each minute using a time-sampling technique. Additionally, lick-by-lick records of the microstructural pattern of sucrose intake were made during the first 15 min of each test for five rats receiving 3 and 10 microg of GLP-1. GLP-1 decreased sham-fed intake by as much as 50%, but GLP-1 did not terminate sham feeding. The frequency of observations of feeding was decreased, but the frequency of resting, the terminal item in the behavioral sequence of postprandial satiety in real feeding rats, did not reliably increase. No abnormal behaviors were observed. Although GLP-I did not affect the latency to begin sham feeding, it significantly reduced the initial rate of licking. GLP-I did not affect the motor aspects of licking, because the interlick intervals within individual bursts of licking or overall lick efficiency were normal. These data suggest that intracerebroventricular infusions of GLP-1 inhibit sham feeding by decreasing the orosensory positive feedback that drives licking, rather than by activating physiological satiating mechanisms or nonspecific mechanisms such as aversion or motor incapacity.

Animals↗

PubMed1998

Regional localization of specific [125I]leptin binding sites in rat forebrain.

Specific [125I]leptin receptor binding sites have been identified in choroid plexus (CP), but have eluded regional localization within the brain parenchyma. To optimize specific [125I]leptin binding in brain loci, we ran experiments varying the pH of incubation buffers. We found that specific [125I]leptin binding in CP was strikingly pH dependent with the most acidic buffer, pH 5.5, resulting in a greater than 100% increase over the amount of specific binding measured at pH 7.5. While low pH permitted detection of specific binding in parenchymal loci, clear pH dependency was only observed in the CP. In the caudate putamen (CauP), a locus with low specific binding, values for specific binding did not differ significantly across the range of pH conditions tested. Using incubation buffers at pH 6.0 in subsequent binding experiments, we localized specific [125I]leptin binding in several brain loci including thalamus and hypothalamus. In CP and thalamus, where the range of OD permitted analysis of binding parameters, [125I]leptin binding was saturable with increasing concentrations of unlabelled leptin. In all loci, specific [125I]leptin binding was insensitive to competition by high concentrations of other unlabelled compounds. Our results varying pH conditions of the incubation buffer suggest leptin receptors may be divided into subclassifications based on pH sensitivity of the specific binding. Furthermore, our results suggest that although densities are low, high affinity leptin receptors are present in neural loci implicated in food intake and energy balance, and are more widespread in the forebrain than previously determined.

Animals↗

PubMed1998

Intracerebroventricular angiotensin II increases intraoral intake of water in rats.

Ad lib and intraoral intake tests can separate the effects of drugs on the appetitive and consummatory phases of ingestive behavior. Central angiotensin II increases ad lib intake from water bottles, but its effect on intraoral intake has not been examined. Rats with both lateral intracerebroventricular (i.c.v.) cannulas and intraoral catheters were given angiotensin II (100 ng/5 microliters i.c.v.) followed by a 10-min intraoral infusion of water. Angiotensin II increased intraoral intake and increased ad lib water intake from bottles after the intraoral test. Thus angiotensin II increases water intake during both appetitive and consummatory phases of drinking.

Angiotensin II↗

PubMed1997

The effect of centrally administered CCK-receptor antagonists on food intake in rats.

Cholecystokinin (CCK) receptors are classified as two subtypes, designated CCK(A) and CCK(B), and both subtypes are found in brain and peripheral tissues of rats. CCK-8 has been shown to act peripherally to reduce meal size, and this satiating action can be blocked by CCK(A)-receptor antagonists. Recent evidence suggests that, in addition to the peripheral action of CCK, central CCK mechanisms may also be involved in satiety. Central administration of proglumide, a mixed CCK-receptor antagonist (CCK(A) > CCK(B)) has been shown to increase food intake and block the satiating effect of peripherally administered CCK-8 (15). In an attempt to replicate and extend these results, rats were given injections of proglumide or selective CCK-receptor antagonists into the lateral ventricle prior to a peripheral injection of CCK-8 or saline. Only proglumide stimulated an increase in 30-min test meal intake and attenuated the satiating effect of CCK-8. Two selective CCK(A)-receptor antagonists, lorglumide and devazepide, did not increase intake significantly when given alone, and they did not attenuate the effect of peripherally administered CCK-8. The selective CCK(B)-receptor antagonist, L365,260, reduced intake at all doses tested except the lowest. The lowest dose did not increase intake when given alone and did not attenuate the inhibitory effect of CCK on test-meal intake. Finally, a combination of devazepide and L365,260 did not increase intake or block the effect of peripherally administered CCK-8. These results suggest that CCK released by neurons in the brain and acting on central CCK(A)- and CCK(B)-receptors is not necessary for the control of meal size or for the satiating effect of peripherally administered CCK-8 in rats under our experimental conditions.

Animals↗

PubMed1996

The increased satiating potency of CCK-8 by estradiol is not mediated by upregulation of NTS CCK receptors.

Estradiol benzoate (EB) increases the satiating effect of CCK-8 in ovariectomized rats. It is possible that this effect of EB is due to upregulation of CCKA receptors in the terminals of vagal afferent fibers because these receptors have been implicated in the mediation of the satiating effect of intraperitoneally injected CCK-8. To test this hypothesis, we used in vitro quantitative autoradiography to measure the effects of EB on the binding characteristics of CCK receptors in the nucleus tractus solitarius (NTS), a region that contains central terminal projections of abdominal vagal afferent fibers. As additional measures of EB's effects on CCK receptors, we also characterized EB's effects on CCK.8 binding in the area postrema (AP), a brain region rich in CCKA receptors, the ventromedial hypothalamus (VMH), a region rich in CCKB receptors, and in the pancreas, a gland rich in CCKA receptors. Saturation binding experiments were run using [125I]CCK-8 (approximately 40 pM, 2200 Ci/mmol) and 0.1-100 nM unlabelled CCK-8. EB did not change the number (Bmax) or affinity (Kd) of CCK receptors in the NTS. Furthermore, competition experiments with 500 nM of the selective CCKA receptor antagonist devazepide or the selective CCKB antagonist L365,260 demonstrated that EB failed to affect CCK receptor subtype number in the medial and lateral divisions of the NTS. EB also did not affect binding in the AP or VMH. These results do not confirm our hypothesis. The lack of effect of EB on vagal CCKA receptors in the NTS was not due to inappropriate conditions of tissue sampling or autoradiographic technique because EB increased the number, but not the affinity, of CCKA receptors in the pancreas significantly.

Animals↗

PubMed1996

A transgenic mouse model to study transsynaptic regulation of tyrosine hydroxylase gene expression.

Previous studies demonstrated that 9 kb of the rat tyrosine hydroxylase (TH) 5' flanking sequence directed appropriate spatiotemporal expression of a lacZ reporter gene to catecholaminergic cells in the CNS of transgenic mice. In the present study, specificity of transgene expression was further extended to demonstrate cell type-specific functional regulation of lacZ expression using manipulations known to alter endogenous TH expression. Alterations in lacZ reporter expression should parallel changes in endogenous TH levels if the DNA elements mediating these functional changes of TH expression in vivo reside within the 9 kb of the TH promoter region. Naris closure induced an activity-dependent decrease of TH expression in dopaminergic periglomerular cells in the olfactory bulb that was paralleled by down-regulation of lacZ expression in the transgenic mice. Densitometry and image analysis were used to quantify lacZ expression following acute reserpine administration (5 mg/kg s.c.), which up-regulates endogenous TH. At 48 h postinjection, analysis of OD values indicated a significant increase of X-gal staining in the locus coeruleus and ventral tegmental area but not in the substantia nigra or olfactory bulb of reserpine-treated transgenic animals. These data showed that the 9-kb sequence also mediates cell type-specific transsynaptic regulation of reporter gene expression. Analysis of this transgenic animal offers a useful model system to study in vivo regulation of TH gene expression.

Animals↗

PubMed1994

Lack of NPY-induced feeding in cobalt protoporphyrin-treated rats is a postreceptor defect.

The administration of cobalt protoporphyrin results in transient decreases in food intake and prolonged weight loss in rats. After IVC injection of cobalt protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated control rats within 48 h. At the same time, the concentrations of mRNA for neuropeptide Y increase approximately twofold in the hypothalamus. The failure of these animals to display a feedings response to elevation of endogenous NPY concentration is mimicked by their failure to respond to exogenous. ICV injections of neuropeptide Y. Because NPY binding studies are confounded by high nonspecific binding, radiolabeled PYY was used to measure binding to hypothalamic membranes and for autoradiography with hypothalamic sections. No abnormalities in the number of receptors or the affinity of the binding interaction were noted. In addition, hypothalamic concentrations of cyclic AMP were unchanged following treatment with either cobalt protoporphyrin or NPY. These results indicate that the locus of the failure of CoPP-treated animals to feed after administration of NPY must be either distal to, or unrelated to, the NPY receptor in the hypothalamus.

Animals↗

PubMed1993

Characterization of type A and type B CCK receptor binding sites in rat vagus nerve.

We employed quantitative receptor autoradiography to analyze pharmacological properties of 125I-Bolton Hunter cholecystokinin (CCK-8)-labeled binding sites in sections of rat cervical vagus nerve that had been ligated 24 h prior to extraction. Binding densities were detected in segments of nerve proximal and distal to the ligature. Analysis was confined to proximal segments. Saturation and competitive binding studies were carried out using sulphated CCK-8 and two selective CCK receptor antagonists: MK-329, to define type-A (CCKA) binding sites; and, L-365,260, to define type-B (CCKB) binding sites. Sulphated CCK-8 was the most potent inhibitor of vagal 125I-CCK binding (IC50 = 2 nM). Nonlinear curve fitting analysis of the CCK binding data favored the presence of a single class of vagal CCK receptors (KDi = 1 nM). However, both MK-329 (IC50 = 18 nM) and L-365,260 (IC50 = 45 nM) competed for vagal 125I-CCK binding indicating the presence of CCKA and CCKB binding sites. Co-analysis of the antagonist binding data suggested that CCKA and CCKB receptors were transported in equal concentrations within the vagus. MK-329 bound with high affinity to CCKA sites (Ki = 3 nM) and low-affinity to CCKB sites (Ki = 462 nM) while L-365,260 bound with high affinity to CCKB sites (Ki = 10 nM) and low-affinity to CCKA sites (Ki = 775 nM). These same ligands were used to characterize the specificity of 125I-CCK binding in the medial and lateral divisions of the nucleus of the solitary tract (NTS), two regions innervated by primary vagal afferents carrying CCK receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Characterization of axonally transported [125I]PYY binding sites in rat vagus nerve.

Quantitative receptor autoradiography was used to characterize [125I]PYY binding to slide-mounted sections of rat cervical vagus nerve which had been ligated 24 h prior to extraction. Saturation and competitive binding characteristics were determined for the accumulation of binding sites detected in the segment of the nerve proximal to the ligature. High and low affinity binding components were resolved (Kd = 93 pM and 2.1 nM). The rank order of potency for competing ligands was PYY greater than NPY much greater than PYY13-36 much greater than [Pro34]NPY suggesting that vagal PYY/NPY binding sites are PYY-preferring and of the Y2 type.

Animals↗

PubMed1990

Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors.

We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain. In addition, both peptides increased water intake when food was present but not when food was absent, suggesting that a neural substrate supporting a direct action of NPY and PYY on water intake is not present in the hindbrain. In time sampling of behaviors occurring during a 90-min feeding test, we found that both peptides increased the time spent eating and reduced grooming. In addition PYY, but not NPY, reduced apparent sleep and increased exploratory activity. This suggests that PYY, but not NPY, influences a hindbrain neural substrate involved in sleep and activity.

Animals↗

PubMed1990

Evidence for separate receptors for insulin and insulin-like growth factor-I in choroid plexus of rat brain by quantitative autoradiography.

Binding of insulin and insulin-like growth factor-I (IGF-I) to the choroid plexus was quantitatively characterized using autoradiography and computer densitometry. Slide-mounted brain slices were incubated in 0.1 nM [125I]-insulin or [125I]-[Thr59]IGF-I. To determine specificity of the binding sites, the labeled peptides were mixed with unlabeled analogues. Autoradiography was done with LKB Ultrofilm and analyzed with a computer image analysis system and program for densitometry. Results showed that binding was time and temperature dependent and reversible. Binding of the iodinated insulin and IGF-I was inhibited by unlabeled peptides in a dose-dependent manner. The rank order of potency of these peptides in competing for the choroid plexus iodoinsulin binding sites was: chicken insulin greater than porcine insulin greater than desoctapeptide insulin greater than IGF-I. IGF-I was more potent than porcine insulin in competing for the choroid plexus iodolGF-I binding sites. Somatostatin was ineffective. Non-linear regression analysis revealed the presence of high- (Kd 1.3 +/- 0.2 nM) and low-affinity (Kd 36 +/- 1.4 nM) binding sites for insulin and a single high-affinity binding site (Kd 3.1 +/- 0.3 nM) for IGF-I in the choroid plexus. There were approximately 50 times more binding sites (Bmax) for IGF-I than for insulin high-affinity sites, whereas the number of low-affinity sites for insulin was about equal to the number of IGF-I high-affinity sites. The results of these binding studies with iodinated insulin and [Thr59]IGF-I support the conclusion that the rat choroid plexus has separate high-affinity receptors for insulin and IGF-I, and that the IGF-I receptors outnumber the insulin receptors.

Animals↗

PubMed1988

Localization of binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by quantitative autoradiography.

In vitro quantitative autoradiography was used to localize IGF-I binding sites in rat brain. Slide-mounted sections of frozen rat brain were incubated in 0.01 nM 125I[Thr59]IGF-I, alone or mixed with 10 nM unlabeled [Thr59]IGF-I or insulin, for 22 h at 4 degrees C and apposed to LKB Ultrofilm. Measurement of labeled [Thr59]IGF-I binding by computer digital image analysis of the autoradiographic images indicated that high affinity IGF-I binding sites are widely distributed at discrete anatomical regions of the brain microarchitecture. The highest concentration of specific binding sites was in the choroid plexus of the lateral and third ventricles. Unlabeled porcine insulin was less potent than unlabeled IGF-I in competing for binding sites on brain slices. Regions of the olfactory, visual, and auditory, as well as visceral and somatic sensory systems were labeled, in particular the glomerular layer of the olfactory bulb, the anterior olfactory nucleus, accessory olfactory bulb, primary olfactory cortex, lateral-dorsal geniculate, superior colliculus, medial geniculate, and the spinal trigeminal nucleus. High concentrations of IGF-I-specific binding sites were present throughout the thalamus and the hippocampus, (dentate gyrus, Ca1, Ca2, Ca3). The hypothalamus had moderate binding in the paraventricular, supraoptic, and suprachiasmatic nucleus. Highest binding in the hypothalamus was in the median eminence. The arcuate nucleus showed very low specific binding, approaching the levels found in optic chiasm and white matter regions. Layers II and VI of the cerebral cortex also had moderate IGF-I binding. The results suggest that the development and functions of brain sensory and neuroendocrine pathways may be regulated by IGF-I.

Animals↗

PubMed1988

Characterization of insulin-like growth factor I receptors in the median eminence of the brain and their modulation by food restriction.

High affinity binding sites for 125I-labeled [Thr59]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slide-mounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr59]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h. Densitometry by computer digital image analysis of autoradiographic images indicated that specific binding of iodo-[Thr59]IGF-I to the median eminence was reversible. The specificity of binding was evaluated with competition of iodo-[Thr59]IGF-I with unlabeled [Thr59]IGF-I, rat IGF-II (multiplication-stimulating activity), and porcine insulin. All were recognized by the binding site, but the rank order of potency was [Thr59]IGF-I greater than IGF-II greater than insulin. Somatostatin was completely ineffective. Further, an antibody against the rat IGF-II receptor did not block binding of iodo-[Thr59]IGF-I to the median eminence. Fourteen days of food restriction (75% of food intake of controls) resulted in significant weight loss and reduction of plasma immunoreactive IGF-I in six food-restricted rats (0.9 +/- 0.1 U/ml) compared with values in six controls (2.6 +/- 0.5 U/ml; P less than 0.001). Binding of 125I-labeled [Thr59]IGF-I in the median eminence was significantly increased in the food-restricted rats, primarily due to an increase in the concentration of iodo-[Thr59]IGF-I-binding sites in the median eminence; the affinity (Kd) of binding was unchanged. The results indicate that the median eminence has type I IGF-I receptors, which become more numerous under metabolic conditions associated with decreased caloric intake and lowered plasma IGF-I levels.

Animals↗

PubMed1986

Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography.

In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arcuate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence. The results are consistent with the hypothesis that insulin modulates the neural regulation of feeding by acting at sites in the hypothalamus.

Animals↗

PubMed1986

An inexpensive microcomputer digital imaging system for densitometry: quantitative autoradiography of insulin receptors with 125I and LKB Ultrofilm.

This article describes a video digitizing system designed for measuring film optical density. The system, which is based on a 6-bit (64 gray level) digitizer, solid state video camera, and Apple II microcomputer, digitizes a rectangular area selected by the operator and converts the gray level values into preselected standard units. In order to develop autoradiographic standard curves for quantitative autoradiography with 125I-insulin, liver slices labeled with 125I-insulin and plastic sections containing known amounts of tritium were apposed to the same sheet of LKB Ultrofilm for exposures of 1-7 days. The results indicate that 3H plastic standards can be used to calibrate QAR of 125I-labeled ligands with LKB Ultrofilm. The Apple system was also used to measure binding of 125I-insulin to the external plexiform layer (EPL) in slices of the rat olfactory bulb. Results suggest that the EPL has two binding sites for insulin, a high affinity site with Kd = 1.0 X 10(-8) M and a low affinity site having a Kd = 1.4 X 10(-5) M.

Animals↗