Biomedical subjects

S P Kalra

Publications and source records attributed to S P Kalra.

At least 19 recordsLinked to original sources

PubMed1992

Evidence that long-term estrogen treatment disrupts opioid involvement in the induction of pituitary LH surge.

Recent evidence suggests that a decrease in the inhibitory opioid influence is a necessary hypothalamic neural event in the preovulatory and ovarian steroid-induced luteinizing hormone (LH) surge. Whether shifts in ovarian steroidal milieu disrupts this neural event is not known. Therefore, the effects of short-term (3 days) and long-term (13 or 17 days) estradiol 17 beta (E2) exposure on spontaneous, naloxone (NAL) and progesterone (P)-induced LH surges were assessed in ovariectomized (ovx) rats. Two weeks after ovariectomy, rats received subcutaneous Silastic capsules filled with crystalline E2. In rats exposed to E2 for 3 days and infused with saline intravenously between 11.00-14.00 h, plasma LH rose significantly at 17.00 h. NAL infusion between 11.00-14.00 h in these rats to decrease the inhibitory opioid influence, advanced both the onset of LH rise and amplified the secretion of LH in the afternoon. Continuation of E2 exposure for 13 days produced no deleterious effects on either the spontaneous or NAL-induced augmentation in LH responses. However, uninterrupted E2 exposure for 17 days abolished the spontaneous afternoon LH rise and drastically diminished the ability of NAL to advance and amplify the LH response. In the next experiment, we evaluated the effect of P injection (2 mg/rat) at 11.00 h on the afternoon LH release in rats similarly exposed to E2 for either 3 or 17 days. In rats exposed to E2 for 3 days, the P-induced LH release was significantly greater than that observed after saline or NAL infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

A selective sexually dimorphic response in the median eminence neuropeptide Y.

Recent studies show that neuropeptide Y (NPY) is widely distributed in the hypothalamus and that it stimulates luteinizing hormone-releasing hormone (LHRH) release from the medial basal hypothalamus (MBH) of male and female rats. The neuroendocrine factors that regulate NPY neurosecretion in two sexes are not well understood. We have previously observed that orchidectomy (orch) in male rats decreased and testosterone (T) replacement increased NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC) and ventromedial nucleus (VMN) and the KCl-evoked in vitro release of NPY from the MBH was likewise decreased after orch and restored by testosterone replacement. Now we report that these NPY responses are different in female rats following removal of the ovaries. Ovariectomy (ovx) decreased NPY concentrations in the ARC and VMN and not in the ME. Estrogen replacement restored NPY concentrations in the ARC and VMN, however, in the ME NPY concentration decreased significantly. Further, the KCl-evoked NPY release in vitro from either the MBH or ME of intact and ovx rats was similar. In an additional concurrent comparative study in male and female rats, we observed that of the 6 microdissected hypothalamic sites, NPY levels were approximately 50% less in the ME of intact females than in those of intact male rats. Again, in male rats there was a significant decrease in NPY levels in the ME, ARC and VMN after orch, whereas in female rats, NPY levels in the ARC and VMN, but not in the ME decreased after ovx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

In vivo pulsatile LHRH release into the anterior pituitary of the male rat: effects of castration.

The effects of castration on the concentration of luteinizing hormone releasing hormone (LHRH) in the anterior pituitary (PIT) was studied in freely-behaving male rats using a push-pull cannula for sampling. In over 70 perfusions of the PIT of rats sampled before and at multiple days after castration there was no consistent change detected in the overall amount, secretory pulse amplitude or frequency or the LHRH signal reaching the PIT.

Animals↗

PubMed1992

Hypothalamic neuropeptide Y gene expression in rats on scheduled feeding regimen.

Recent evidence suggests that neuropeptide Y (NPY) is an important signal in the neural circuitry that controls feeding behavior. Previously we observed that in rats entrained to 4 h daily scheduled feeding regimen (SFR), NPY content and release in the paraventricular nucleus (PVN) was elevated but decreased rapidly in association with food consumption. In the present study, we investigated the pattern of hypothalamic NPY gene expression in SFR rats before and after food consumption by measuring the content of preproNPY mRNA in the medial basal hypothalamus (MBH). Adult male rats were maintained on either ad libitum diet (control) or on SFR. Rats were killed before food presentation at 11.00 h and at the end of 4 h food consumption at 15.00 h. The levels of preproNPY mRNA in the MBH were determined by solution hybridization/RNase protection assay using a cRNA probe complementary to rat NPY precursor mRNA. We observed that, as compared to that in control rats on ad libitum diet, preproNPY mRNA levels in the MBH were increased two-fold in the SFR rat at 11.00 h and remained elevated even after 4 h of food consumption. These results show a simultaneous enhancement in PVN NPY release and hypothalamic gene expression in advance of scheduled feeding time, but food intake rapidly decreases PVN NPY release and content, with little impact on hypothalamic gene expression.

Animals↗

PubMed1992

Effect of d-fenfluramine on neuropeptide Y concentration and release in the paraventricular nucleus of food-deprived rats.

Recent evidence indicates that Neuropeptide Y (NPY) is an important signal in the hypothalamic neural circuitry that stimulates feeding in the rat. Administration of d-fenfluramine (FEN) has been shown to rapidly inhibit feeding in the rat. Because food deprivation increases the levels and release of NPY in the paraventricular nucleus (PVN) of the hypothalamus, the aim of this study was to investigate whether the rapid anorectic effects of FEN in food-deprived (FD) rats are associated with alterations in the hypothalamic NPYergic system. In the first experiment, the effect of FEN (10 mg/kg) on NPY concentrations in nine microdissected hypothalamic sites was assessed by radioimmunoassay (RIA) in rats either food deprived for 3 days or fed ad lib during the experimental period. In response to food deprivation, NPY concentrations increased significantly in the PVN and arcuate nucleus, but NPY levels remained unchanged in the remaining seven hypothalamic sites. In control rats maintained on ad lib food supply, FEN injection produced little effect on NPY concentration in hypothalamic sites. However, FEN suppressed NPY levels selectively in the PVN of FD rats, so that NPY concentrations measured in the nucleus were within the range found in satiated control rats. In the second experiment, the effect of FEN on NPY release in the PVN was examined in FD rats by the push-pull cannula (PPC) technique. NPY levels in the PPC perfusate were unchanged in FD rats during the period 30-120 min after saline or FEN injection. Also, the mean rate of NPY release was similar in vehicle- and FEN-treated FD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Effects of tachykinins on luteinizing hormone release in female rats: potent inhibitory action of neuropeptide K.

Tachykinins, a family of biologically active related peptides, are found in variable amounts in the rat hypothalamus. We assessed the effects of five tachykinins, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK), neuropeptide gamma (NP gamma), and neurokinin B (NKB), on LH release in different experimental model systems in ovariectomized rats. In the first series of experiments rats were ovariectomized and implanted with permanent cannulae in the third cerebroventricle of the rat brain. Two weeks later, the effects of intracerebroventricular injection of 0.5 or 1.25 nm various tachykinins on LH release were studied. The results showed that whereas SP, NKA, and NKB were ineffective, and NP gamma was marginally effective, NPK produced a long-lasting suppression of LH release. NPK decreased LH release in a dose- and time-related fashion. Similarly, in the second series of experiments, whereas SP and NKA were inactive, NPK completely suppressed the LH surge induced by progesterone in estrogen-primed ovariectomized rats. In the third series of experiments we observed that NK-2 receptor agonist [Nle10]NKA4-10, and not NK-1 receptor agonist [Sar9,Met(O2)11]SP, suppressed both the release of LH in vivo and basal and KCl-induced hypothalamic LHRH release in vitro. These results show that NPK is the most effective tachykinin in suppressing LH release, and the inhibitory response is mediated by hypothalamic NK-2 receptors. These findings are in accord with the hypothesis that NPK may serve as a hypothalamic inhibitory neurotransmitter/neuromodulator of LHRH secretion.

Animals↗

PubMed1992

Involvement of the Y-1 receptor subtype in the regulation of luteinizing hormone secretion by neuropeptide Y in rats.

The present experiments were designed to investigate structure-function relationships, and identify the receptor subtype and postreceptor cellular mechanisms that mediate the ovarian hormone-dependent, excitatory, and inhibitory effects of neuropeptide Y (NPY) on LH release in female rats. Intracerebroventricular administration of NPY decreased plasma concentrations of LH in ovariectomized, hormonally untreated rats but stimulated LH release in ovariectomized rats pretreated with estradiol benzoate and progesterone. A similar dual response was also obtained after administration of NPY2-36. However, deletion of additional amino acids at the N terminus, as in NPY5-36, NPY11-36, NPY16-36, and NPY25-36, rendered the peptides inactive. An N-terminal fragment, NPY1-24-amide, and a discontinuous NPY analog, NPY1-4-epsilon-amino-caproic acid-25-36, similarly failed to influence LH release. The analog [Leu31,Pro34]NPY, a preferential agonist at the Y-1 NPY receptor subtype, also elicited the dual LH responses, but the preferential Y-2 receptor agonist, NPY13-36, was completely inactive. Further, only the peptides that stimulated LH release in vivo, i.e. NPY, NPY2-36, and [Leu31,Pro34]NPY, also stimulated the release of LHRH from median eminence fragments of steroid-primed rats in vitro, and the excitatory effect of [Leu31,Pro34] NPY was blocked by a noncompetitive NPY receptor antagonist, D-myo-inositol-1,2,6-trisphosphate. With the exception of NPY1-24-amide, all of the NPY fragments tested bound specifically to NPY binding sites in hypothalamic membrane preparations, but the highest binding affinities were found for the peptides that evoked biological responses in the in vivo and in vitro tests. Further analysis of the mode of action of NPY showed that the stimulation of LHRH release in vitro was unaffected by omission of Ca2+ from the incubation medium, but was prevented by two antagonists of intracellular Ca2+ mobilization, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester and ryanodine. Inhibition of prostaglandin synthesis with indomethacin blocked the stimulatory effect of the alpha 1-adrenergic agonist methoxamine on LHRH release, but not the increase produced by NPY.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

PubMed1992

Steroidal regulation of hypothalamic neuropeptide Y release and gene expression.

Neuropeptide Y (NPY) readily stimulates the release of hypothalamic LHRH and pituitary LH release in intact and gonadal steroid-primed gonadectomized rats. We have now tested the hypothesis that the release and synthesis of hypothalamic NPY may be regulated by gonadal steroids. To measure the effects of gonadal hormones on NPY release, a permanent push-pull cannula was implanted in the anterior pituitary (AP) of sham castrated (controls) or castrated (CAST) male rats, and 1 week later, the AP was perfused with artificial cerebrospinal fluid over a 3-4 h period. NPY concentrations in the perfusates collected at 10-min intervals were measured by RIAs. The NPY release pattern in the AP was episodic in both intact and CAST rats, and the frequency of NPY episodes was similar in two groups. However, the amount of NPY detected in the AP of CAST rats was significantly less than that of intact rats because the mean rate of release and the amplitude of NPY episodes in the perfusates of CAST rats were significantly reduced. This observation of attenuated hypothalamic NPY output in vivo and previous evidence of decreased hypothalamic NPY contents after CAST implied that the synthesis of hypothalamic NPY may be regulated by testicular secretions. Therefore, the effects of testosterone (T)-replacement on preproNPY messenger RNA (mRNA) in the medial basal hypothalamus (MBH) was evaluated. Rats were CAST and received either empty or T-filled Silastic capsules sc. Two weeks later, the level of perproNPY mRNA in the MBH was determined by solution hybridization/ribonuclease protection assay using a complementary RNA probe complementary to the rat NPY precursor mRNA. We observed that the levels of preproNPY mRNA were 2-fold higher in the MBH of T-replaced CAST as compared to control CAST rats. These findings are consistent with the hypothesis that gonadal steroids enhance the neurosecretory activity of hypothalamic NPYergic neurons, and for the first time reveal a coupling between the level of gene expression and the secretion of a neuropeptide involved in the regulation of hypothalamic LHRH and pituitary LH release.

Animals↗

PubMed1992

Neuropeptide Y release is elevated from the microdissected paraventricular nucleus of food-deprived rats: an in vitro study.

Intracerebroventricular injection of neuropeptide Y (NPY) stimulates a robust dose-related feeding response in the rat. Experimental evidence attests to the view that the release of NPY in the paraventricular nucleus (PVN), a site richly innervated by NPY immunopositive fibers, is responsible for stimulation of feeding behavior. However, there is little information on the neuroendocrine factors involved in regulation of NPY release, in part due to the unavailability of reliable techniques to monitor PVN NPY release. In this study, we have validated an in vitro technique to assess NPY release from the PVN and other neighboring hypothalamic sites of the rat brain. In the first experiment, freshly dissected brains from male rats were processed for 300-microns thick sections with a vibratome. The PVNs were microdissected from the brain sections under a stereomicroscope and incubated in 250 microliters Krebs Ringer bicarbonate buffer at 37 C for basal and KCl-induced NPY release. The results showed that basal NPY efflux from the excised PVN was detectable and increased in relation to the number of PVNs in the incubation chambers. Addition of KCl at the end of the 60-min basal incubation period increased NPY release further, the increments were again closely related to the number of PVN punches in the incubation chambers. In the second experiment, the assumption that in vitro basal and KCl-evoked NPY release from the PVN reflected the in vivo pattern of PVN NPY secretion was validated. The effects of 4-day food deprivation (FD), an experimental paradigm known to augment in vivo PVN NPY secretion, on the in vitro NPY release from PVN and ventromedial nucleus were evaluated. The results showed that both basal and KCl-evoked NPY release was significantly higher from the PVN of food-deprived than control rats on ad libitum rat chow. This FD-induced incremental NPY response was site-specific because the basal and KCl-evoked NPY effluxes from the ventromedial nucleus of FD and control rats were similar. Thus, in agreement with previous in vivo findings, NPY release in vitro is also augmented selectively from the PVN in response to fasting. Cumulatively, these results demonstrate that NPY release in vitro from hypothalamic sites microdissected from fresh brains can be assessed in a reliable fashion and are in accord with the proposal that enhanced NPY action within the PVN is responsible for increased drive for food.

Animals↗

PubMed1992

Diverse effects of tachykinins on luteinizing hormone release in male rats: mechanism of action.

The tachykinins are a group of structurally related peptides found in the rat hypothalamus and anterior pituitary. We have evaluated the effects of four tachykinins on LH release in male rats. In intact male rats, intracerebroventricular (icv) injection of neurokinin A (NKA), neuropeptide K (NPK), and neuropeptide-gamma (NP gamma) elicited dose-related, transient increases in plasma LH. Substance P (SP) was ineffective under these conditions. A further examination showed that in vitro incubation with either NPK or NP gamma of hemipituitaries from intact but not castrated male rats promoted release of LH into the medium, thereby revealing that the excitatory effects of tachykinins in intact male rats may, in part, be a result of stimulation of LH release directly from the anterior pituitary. On the other hand, the effects of these four tachykinins on LH release were different in castrated rats. Intracerebroventricular injection of NPK, NKA, and NP gamma as well as SP, which was ineffective in intact male rats, evoked a long-lasting suppression of LH release. Comparatively, NPK was the most effective tachykinin in eliciting LH responses in both of these tests involving different endocrine environments. We next evaluated the possibility that the inhibitory effects of tachykinins (NPK) may be mediated by activation of inhibitory endogenous opioid peptides. The results showed that iv infusion of the opiate receptor antagonist naloxone, to block the possible inhibitory effects of endogenous opioid peptides, only partially counteracted the suppressive effects of icv NPK on plasma LH levels. Thus, in addition to revealing the diverse effects of structurally related tachykinins on LH release, the results of these investigations showed specifically that the NK-2 receptor agonists NPK, NP gamma, and NKA stimulated LH release in intact rats, in part, by a direct action at the level of the pituitary, whereas the NK-1 receptor agonist SP was inactive under these conditions. These findings imply a paracrine/autocrine mode of excitatory action on LH release involving pituitary NK-2 receptor subtypes. On the other hand, in castrated rats, all four tachykinins readily suppressed LH release by a central action involving, in part, an activation of hypothalamic opioid systems.

Animals↗

PubMed1992

Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis.

Central administration of neuropeptide-Y (NPY) inhibits pituitary LH release in ovariectomized rats and stimulates LH release in intact and ovariectomized rats pretreated with ovarian steroids. Although the precise neural mechanism of this dual effect of NPY is not known, experimental evidence suggests an underlying interaction between hypothalamic NPY and the inhibitory beta-endorphin (beta END) systems in the neuroendocrine regulation of pituitary LH release in the rat. The present study was undertaken to examine the morphological basis of the interaction between these two peptidergic systems in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine-pretreated female rats were double immunostained for NPY and beta END and examined by light and electron microscopy. The light brown diaminobenzidine reaction was used to visualize beta END cells, while NPY neurons were labeled with a dark blue nickel ammonium sulfate-intensified diaminobenzidine reaction. Under the light microscope, a dense network of NPY-immunoreactive axons and axon terminals was observed in close apposition with beta END-immunoreactive neurons throughout the medial basal hypothalamus. Electron microscopic examination revealed that NPY-immunoreactive boutons formed axosomatic and axo-dendritic synaptic connections with beta END cells. A majority of these synaptic membrane specializations appeared asymmetrical [corrected]. In light of the previous evidence of excitatory and inhibitory effects on LH release and the existence of direct synaptic connections between NPY and LHRH neurons in the hypothalamus, the current results imply that the dual effects of NPY on LH secretion may involve modulation of LHRH secretion, both by the direct route and indirectly through the hypothalamic beta END system.

3,3'-Diaminobenzidine↗

PubMed1992

Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats.

We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ)-induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN. Evaluation of NPY release in vitro showed that both basal and KCl-induced release was significantly higher from the micro-dissected PVN of STZ-treated than control rats. A similar augmentation in the NPY efflux in vitro was detected from the median eminence arcuate nucleus, but not from the neighboring ventromedial nucleus of STZ-treated rats. In the second experiment, rats were treated with STZ or vehicle and received permanent push-pull cannula (PPC) in the PVN for evaluation of NPY release in vivo 18-21 days after STZ treatment. The results showed that mean NPY levels in the perfusates collected from the PVN of diabetic rats were significantly higher as compared to control rats. Since NPY is the most potent naturally occurring orexigenic signal and the PVN is an important initial site of NPY action in the stimulatory pathway regulating feeding, our findings of augmented PVN NPY release in vivo and in vitro are in accord with the hypothesis that increased NPY secretion in the PVN may be responsible for hyperphagia in diabetic rats.

Animals↗

PubMed1992

Neuropeptide Y: a novel neuroendocrine peptide in the control of pituitary hormone secretion, and its relation to luteinizing hormone.

Evidence that establishes neuropeptide Y (NPY) as an important neuromessenger in the regulation of anterior pituitary hormone secretion is reviewed. In particular, NPY plays a critical role in stimulating the episodic, basal pattern of luteinizing hormone (LH) release, as well as the preovulatory surge of LH release in several species. The stimulatory effect of NPY on LH secretion is dependent upon the presence of gonadal hormones and involves amplification of the response of other interacting stimulatory signals. NPY acts at the level of the median eminence to excite the release of LH-releasing hormone (LHRH) via a mechanism that leads to the mobilization of intracellular Ca2+. These stimulatory LHRH responses are mediated by Y1NPY receptors. Moreover, NPY activates postsynaptic messenger pathways that complement and reinforce those affected by norepinephrine, which is another major neuroregulator of LHRH secretion and which is released as a cotransmitter with NPY in the median eminence. Additionally, NPY is released into the hypophyseal portal blood for transportation to the anterior pituitary where it enhances the release of LH in response to LHRH. This facilitatory, modulating effect at the pituitary level involves an allosteric increase in LHRH binding to its receptor leading to augmented influx of Ca2+ from the extracellular space. There is evidence that gonadal steroids regulate NPY neurosecretion in a site-specific manner, and that alterations in NPY secretion may occur in part via a direct action of the steroids on NPY neurons in the brainstem and hypothalamus and in part through an indirect effect involving removal of the inhibitory influence of endogenous opioid peptides. These findings are integrated into an overall hypothesis for induction of the preovulatory LH surge on proestrus requiring an interplay between NPY and other neuronal networks. In aged male rats, due to the inability of hypothalamic NPY neurons to respond appropriately to the trophic effects of androgens, NPY neurosecretion is diminished. Further, a review of the literature reveals that NPY may modulate the secretion of other pituitary hormones through a similar combination of hypothalamic and pituitary actions.

Amino Acid Sequence↗

PubMed1991

Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food.

Feeding in mammals is a periodic behavior; however, knowledge of how the brain signals an intermittent eating pattern is scanty. Recent indirect evidence indicates that one of the signals encoded in the structure of neuropeptide Y (NPY) is to stimulate robust feeding. Therefore, two series of experiments were undertaken to characterize NPY secretion within the paraventricular nucleus (PVN) in association with eating behavior in the rat. Dynamic changes in NPY concentration in several hypothalamic sites and release in the PVN were assessed before and during the course of food consumption in rats trained to eat daily only for 4 h. Only in the PVN were NPY concentrations elevated before the introduction of food and, thereafter, levels decreased significantly during the course of eating. A similar temporal pattern in NPY release into the PVN interstitium was evident in samples collected by push-pull cannula perfusion in unrestrained rats. In addition, in food-deprived rats displaying a robust drive for feeding, NPY release in the PVN was also markedly enhanced in the shape of high-amplitude secretory episodes as compared to a lower release rate in rats receiving food ad libitum. The higher rate of NPY release in fasted rats returned to the control range after 24 h of ad libitum food supply. These findings of intense and dynamic NPY neurosecretory activity within a discrete hypothalamic site in association with an increased drive for food consumption demonstrate that NPY release in the PVN is an important orexigenic signal for periodic eating behavior. These results have important global implications for elucidating the underlying causes of the pathophysiology of eating disorders--anorexia nervosa, bulimia, and obesity--as well as constituting a specific contextual model for the formulation and testing of suitable NPY receptor agonists and antagonists for therapeutic intervention.

Animals↗

PubMed1991

Neuropeptide K (NPK) suppresses copulatory behavior in male rats.

Recent studies show that neuropeptide K (NPK), a member of the tachykinin family of neuropeptides, is found in various hypothalamic sites implicated in the control of gonadotropin secretion, food intake and sexual behavior. Since our previous studies showed that NPK inhibited feeding and gonadotropin secretion in rats, we have now assessed the effects of NPK on sexual behavior in male rats. Copulatory behavior was recorded subsequent to injection of different doses of NPK either into the third ventricle of the brain or intraperitoneally in sexually experienced male rats. We observed that intraventricular (IVT) administration of 0.125 nmol NPK produced only a slight effect on behavior as indicated by a significant increase in intromission latency. However, a four-fold higher dose of 0.5 nmol of NPK completely eliminated copulatory behavior. These rats displayed no overt locomotor deficit but ignored the receptive females, rarely approaching them during the test period. Only two mounts and no intromissions were observed in 6 rats during the test period. In contrast, neither the same dose of 0.5 nmol nor a higher dose of 3.14 nmol injected intraperitoneally produced any discernible effect on sexual performance. These results show that NPK acts centrally to inhibit sexual behavior in male rats and that hypothalamic NPK may be an important part of the neural circuit that regulates reproduction and related behaviors.

Animals↗

PubMed1991

Structure-function analysis of stimulation of food intake by neuropeptide Y: effects of receptor agonists.

Neuropeptide Y (NPY) is a potent natural orexigenic signal in the rat. In this study, we have compared the effects of several COOH-terminal fragments of NPY and NPY receptor agonists on cumulative food intake in male rats. Rats were implanted with permanent cannulae either into the third cerebroventricle or paraventricular nucleus (PVN). NPY1-36 and various COOH-terminal fragments of NPY, two agonist analogues [Leu31, Pro34]NPY and NPY 1-4-Aca (epsilon-amino-caproic acid)-25-36, were administered intracerebroventricularly (ICV) or directly into the PVN, and the cumulative 2-h food intake response was compared. We observed that peptides that were effective by ICV were also effective when administered into the PVN, but smaller amounts of the peptides were required after PVN injection to evoke an equivalent food intake response. Injection of NPY1-36 induced a dose-dependent increment in food intake. Surprisingly, deletion of NH2-terminal tyrosine residue did not adversely affect feeding behavior. In fact, NPY2-36 was consistently more effective than NPY1-36; the enhancement in feeding by NPY2-36 was dose-related and was higher than evoked by NPY1-36 at each dose tested. Further serial deletion of aminoacids at NH2-terminal resulted in complete loss of activity. In addition, NPY agonist analogue, NPY 1-4-Aca-25-36, failed to stimulate feeding. However, NPY Y1 receptor agonist, [Leu31, Pro34]NPY, but not Y2 receptor agonist, NPY13-36, stimulated feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of various tachykinins on pituitary LH secretion, feeding, and sexual behavior in the rat.

Our investigations of the four tachykinines tested have shown that NPK characteristically evoked a spectrum of biological effects in male and female rats. NPK suppressed pituitary LH release by inhibiting the release of hypothalamic LHRH, presumably by activation of NK-2 tachykinin receptor subtypes. However, NPK may also act at the level of gonadotrophs to stimulate LH release in male rats. Central injection of NPK rapidly disrupted copulatory behavior in sexually active male rats. NPK also suppressed feeding, but, in this case, peripheral injections were more effective than central injections. Taken together, these observations strongly imply that NPK may be an inhibitory messenger molecule in the hypothalamic control of reproduction, sexual, and feeding behaviors.

Animals↗

PubMed1991

Sexual function and neuropeptide Y levels in selected brain regions in male spontaneously hypertensive rats.

Sexual function was examined in spontaneously hypertensive rats (SHR) from 8 to 20 wk of age and compared with normotensive Wistar-Kyoto (WKY) and Long-Evans rats (LE). Blood pressures (evaluated indirectly) were elevated in SHR (185 +/- 2 and 195 +/- 3 mmHg at 16 and 19 wk of age, respectively) relative to WKY and LE (135-144 mmHg). SHR exhibited good copulatory behavior but displayed fewer erections (less than 20% of the number displayed by WKY or LE) in ex copula tests. At the conclusion of the study (20 wk of age), body weights were lowest in SHR, intermediate in WKY, and greatest in LE. Relative weights of testes were greater in SHR, whereas relative weights of accessory organs, pituitary and adrenal glands, and kidneys were equivalent across strains, as were circulating levels of aldosterone. Circulating levels of testosterone were higher in SHR and WKY than in LE. Neuropeptide Y (NPY) levels in the median preoptic and arcuate nuclei were significantly greater in SHR than in WKY or LE, whereas NPY levels in the medial preoptic area and the suprachiasmatic, hypothalamic dorsomedial, and hypothalamic paraventricular nuclei were equivalent in SHR and WKY, with both greater than LE. No strain differences were evident in the medial nucleus of the amygdala, the bed nucleus of the stria terminalis, the median eminence, the anterior hypothalamic nucleus, or the hypothalamic dorsomedial nucleus.

Aldosterone↗