Feeding behaviour after injection of α-adrenergic receptor agonists into the median raphe nucleus of food-deprived rats

This study investigated the participation of median raphe nucleus (MnR) α1-adrenergic receptors in the control of feeding behaviour. The α1-adrenergic agonist phenylephrine (PHE) and α2-adrenergic agonist clonidine (CLON) (at equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab chow/day for 7 days. Immediately after the drug injections, the animals were placed in the feeding chamber and feeding and non-ingestive behaviours such as grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The results showed that both doses of PHE injected into the MnR of overnight fasted animals decreased food intake accompanied by an increase in the latency to start feeding. A reduction in feeding duration was observed only after treatment of the MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency increased after injection with the highest dose PHE into the MnR. Feeding frequency and the other non-ingestive behaviours remained unchanged after PHE treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted rats decreased food intake. This hypophagic response was accompanied by a decrease in feeding duration only after treatment of the MnR with the highest dose of PHE. The latency to start feeding and feeding frequency were not affected by injection of either dose of PHE into the MnR. While both doses of PHE increased sniffing duration, the highest dose of PHE increased resting duration and resting frequency. Treatment with CLON into the MnR did not affect feeding behaviour in either of the food deprivation conditions. The present results indicate the inhibitory functional role of α1-adrenergic receptors within the MnR on feeding behaviour.     

Effect of the 5-HT(1A) receptor agonist 8-OH-DPAT on food and water intake in chickens

The effects of the 5-HT(1A) receptor agonist 8-OH-DPAT on food and water intake in 16-week-old male chickens were investigated. Injection of 25 or 50 microg/kg of 8-OH-DPAT 15 min before refeeding starved animals (starved-refed) produced a decrease in food intake 1 h after the start of refeeding. No effect was observed in water intake. The injection of 25 or 50 microg/kg of the 8-OH-DPAT 60 min after the start of refeeding (fed) produced increased food intake, but no effect was observed on water intake. The agonist 8-OH-DPAT (50 microg/kg) injected in water-deprived chickens 15 min before water presentation produced a rapid increase in water intake and an increase in food intake 90 min after the presentation of water. The effect on food intake was mainly apparent 60-90 min after injection. However, when the chickens were water-deprived, the intravenous administration of 8-OH-DPAT 15 min before the presentation of water produced an increase in water intake only 15 min after the start of the experiment. The results show that the effect on food intake of the agonist 8-OH-DPAT in chickens was similar to that observed in mammals. Also, the results show that the agonist-induced increase in water intake may act via a different mechanism. The results show that the 8-OH-DPAT, as in mammals, has a complex effect on food and water intake in chickens and that further works need to be carried out to understand the mechanisms involved in the food and water intake using different animal models.     

Effects of fasting and refeeding on the activity of hepatic glucose-6-phosphatase in rats

The activities of glucose-6-phosphate hydrolase and glucose-6-phosphate translocase were determined in rats fasted for 1-3 days and in animals fasted for one day and then either refed with mixed pellet or given oral or intraperitoneal glucose. The assay was based on the colorimetric measurement of the released inorganic phosphate. Fasting over 24 h significantly increased both the translocase and the hydrolase activity of glucose-6-phosphatase. These parameters showed a further increase when rats were fasted for another 24 h. In animals fasted for 24 h and then refed with standardized pellet diet, a progressive fall of enzyme activity was noticed. However, even 72 h of refeeding did not lead to complete normalization. Glucose given orally or intraperitoneally also suppressed the enzyme activity, although the effect was somewhat delayed. As expected, in fasting rats glucose and insulin levels were significantly decreased. Normoglycaemia was established after just 24 h, regardless of refeeding with pellets or with glucose. The former group exhibited hyper- and the latter hypo-insulinaemic pattern. We speculate that augmented activity of hepatic glucose-6-phosphatase during fasting stimulates the metabolism of glucose through the glucose cycle and is thereby at least partially responsible for insulin resistance accompanying the fasting state.     

Refeeding after the late increase in nitrogen excretion during prolonged fasting in the rat.

Recovery of body mass, food intake and body composition was studied in the laboratory rat after the late increase in nitrogen excretion that characterizes prolonged fasting in mammals and birds. The rats lost 43% of their body mass during 13 days of food deprivation. They all regained their prefasting body mass within a shorter period of 11 days of refeeding. These results confirm that the late increase in nitrogen excretion in rats, as in spontaneously fasting birds, is reversible and is a part of the physiological adaptations to long-term food deprivation. Water intake of the rats continuously decreased during fasting, and the animals virtually stopped drinking as protein utilization increased. On refeeding, changes in water intake paralleled those in food intake. The refed rats progressively increased their daily food intake, that was always higher than the prefasting value (8.0-10.4 vs. 6.7% of body mass). The comparison of organ weights between fed and ad lib refed rats of similar body weight indicates that muscle mass was regained earlier than body fat during refeeding. The laboratory rat therefore appears to be a good experimental model to investigate the metabolic and behavioural changes that occur during spontaneous anorexia and refeeding in wild animals.     

Feeding-dependent depression of melanin-concentrating hormone and melanin-concentrating hormone receptor-1 expression in vagal afferent neurones

Food intake is regulated by signals from the gastrointestinal tract. Both stimulation and inhibition of food intake may be mediated by upper gastrointestinal tract hormones, e.g. ghrelin and cholecystokinin that act at least partly via vagal afferent neurones. We now report that vagal afferent neurones in both rat and man express melanin-concentrating hormone and its receptor, melanin-concentrating hormone-1R. In nodose ganglia from rats fasted for 24 h, RT-PCR revealed the expression of both melanin-concentrating hormone and melanin-concentrating hormone-1R, whereas in ganglia from animals fed ad libitum expression was virtually undetectable. Immunohistochemical studies also revealed expression of melanin-concentrating hormone and melanin-concentrating hormone-1R in nodose ganglion neurones of fasted rats, but signals were weak in rats fed ad libitum. Melanin-concentrating hormone and melanin-concentrating hormone-1R were expressed in the same neurones, a high proportion of which also expressed the cholecystokinin-1 receptor. When fasted rats were refed, there was down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R expression over a period of 5 h. Similar effects were produced by administration of cholecystokinin to fasted rats. The cholecystokinin-1 receptor antagonist lorglumide inhibited food-induced down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R. We conclude that the satiety hormone cholecystokinin acts on vagal afferent neurones to inhibit expression of melanin-concentrating hormone and its receptor. Since the melanin-concentrating hormone system is associated with stimulation of food intake this effect of cholecystokinin may contribute to its action as a satiety hormone.     

Effect of a beta-3 agonist on food intake in two strains of rats that differ in susceptibility to obesity

CONTEXT: Beta-3 agonists acutely reduce food intake, but the mechanism is not well understood. OBJECTIVE: To evaluate the effect of a beta3 agonist on food intake in two strains of rats that differ in their sensitivity to becoming obese while eating a high-fat (HF) diet. METHODS: Male Osborne-Mendel (OM) and S5B/Pl (S5B) rats were treated with a beta3-adrenergic agonist (CL 316,243) at 8 weeks of age, after an adaptation to either an HF (56% fat energy) or a low-fat (LF; 10% fat energy) diet that was equicaloric for protein (24% energy). Ad-lib-fed rats were injected intraperitoneally with CL 316,243, at doses of 0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg, or with vehicle at the beginning of the dark cycle. Food intake was measured at 1, 3, 6 and 24 h after injections. RESULTS: The beta3 agonist CL 316,243 significantly decreased food intake at all timepoints in both strains of rats eating both diets. However, this inhibition of food intake was significantly greater in the S5B rat. CL 316,243 significantly decreased serum leptin and serum glucose in both the OM and the S5B rats, and again, the inhibition was greater in the S5B rat. Whereas CL 316,243 increased serum insulin levels in the OM rat, it decreased them in the S5B rat on an LF diet. In a second experiment, chow-fed rats were implanted with vascular ports into the jugular vein and allowed to recover. When CL 316,243 was injected into the animals that were fasted overnight, rats of both strains significantly increased their serum insulin at 30 min, but the increase was much more pronounced in the S5B rat. Serum glucose was decreased significantly at both the 30- and 60-min timepoints in the OM rat and at 30 min in the S5B rat. CONCLUSION: These experiments demonstrate that a beta3 agonist (CL 316,243) has a much greater effect in a strain of rats that resist fat-induced obesity.     

Physiological and behavioral responses to intermittent starvation in C57BL/6J mice

The dual intervention point model states that body mass is controlled by upper and lower intervention points, above and below which animals (and humans) intervene physiologically to bring their body mass back into the acceptable range. It has been further suggested that the lower intervention point may be defined by the risk of starvation, while the upper intervention point may be defined by the risk of predation. The objective of the present study was to test whether the risk of starvation determines the lower intervention point and to examine the physiological and behavioral mechanisms that underpin the regulation of body mass, when the risk of starvation is increased. Sixty-four mice were exposed to random days of complete fasting or 50% food restriction and their body mass and fat mass responses were measured. Food intake, physical activity and body temperature were measured throughout the experiment. In addition, plasma leptin and insulin, triglyceride and non-esterified fatty acids, along with hypothalamic neuropeptides gene expression in the arcuate nucleus were assessed after 13 and 42 days of treatment. We found that C57BL/6J mice increased body mass and fatness in response to a short-term (13 days) intermittent fasting, which was restored to baseline as the treatment was prolonged. In contrast, intermittently 50% food restricted mice showed no significant changes in body mass or fatness. Over the first 13 days of treatment the data were consistent with the dual intervention point model as the mice showed both increased body mass and adiposity over this period. Over the more protracted period of 42 days the effect waned and was therefore inconsistent with the model. The body mass and fat mass gains in intermittently fasted mice were mainly accounted for by increased food intake. Elevated NPY gene expression after 13 days (three 24 h fasting events) may have driven the increase in food intake. However, no changes were observed in such neuropeptides as POMC, CART, AgRP, Ob-Rb and SOCS 3 or circulating levels of leptin, insulin, NEFA and TG. Hypothermia during fasting days may have also contributed to the increase in body mass. Over 42 days of treatment (nine 24 h fasting events) cumulative food intake was not affected by intermittent starvation. However physical activity, mainly activity during the light phase was lowered suggesting an adaptation to unpredictable starvation. Overall, mice exhibited different behavioral and physiological responses to intermittent starvation depending on the duration of treatment.     

Role of diurnal variation and receptor specificity in the opioidergic regulation of food intake in free-fed and food-deprived rats.

The effects of opioid agonists, morphine (MOR) and ketocyclazocine (KCZ), and antagonists, naltrexone (NALTX) and Mr2266, were investigated on food intake under various conditions, i.e., during light and dark phases of diurnal cycle and free-fed and fasting states in rats. NALTX showed a greater anorexic effect during dark phase, whereas Mr2266 produced such effect during light phase. This suggests that mu-receptors play a major role during dark phase while kappa-receptors are more important in light phase. The comparison of effects of different opioidergic drugs in fasted and free-fed rats showed that NALTX and Mr2266 reduced the elevated basal food intake in 18-h fasted rats to free-fed control levels. Therefore, it appears that enhanced endogenous mu- and kappa-directed neural mechanisms are one of the factors responsible for enhancing food intake in fasted rats. Differential role of MOR and KCZ on food intake in free-fed and fasted rats is also indicated in our study. Both agonists produced a biphasic response in fasted rats, i.e., hyperphagia (0-1 h) followed by hypophagia (1-6 h). However, a generalized hyperphagic effect is observed in free-fed rats (except during 3-6 h by MOR). The initial hyperphagic effect is more prominent in fasted rats which may be due to additive effects of endopioid mechanisms. Specificity of the response at various intervals is confirmed by blockade with NALTX and Mr2266. NALTX appears more potent than Mr2266 in antagonising the effects of MOR but markedly less potent than Mr2266 in inhibiting the effects of KCZ. This suggests that both MOR and KCZ have a mu as well as kappa component in food intake response.     

Repeated fasting/refeeding elevates plasma leptin without increasing fat mass in rats

It is known that repeated fasting and refeeding increase capacity of fat storage in adipose tissue as an adaptive response to fasting. However, the amount of weight gain in fasted/refed animals falls behind the control level in most rodent studies. Leptin, an adipocyte-derived hormone that impacts on energy homeostasis, may be up-regulated by repeated cycles of fasting and refeeding. In this study, we investigated the adaptive response of leptin to repeated cycles of 1-day fasting and 1-day refeeding for 42 days in rats. The repeated fasting and refeeding (RFR) rats gained less body weight than the controls. Daily food intake of the RFR rats was decreased after Day 16 and remained suppressed. Circulating leptin levels of the RFR rats were significantly elevated at Day 35 compared with the controls and at Day 44 compared with the controls and pair-fed (PF) rats. Leptin mRNA levels of these rats were also significantly increased in retroperitoneal white adipose tissue (RT-WAT) compared with the controls and PF rats. Moreover, hypothalamic proopiomelanocortic (POMC) gene expression was augmented in the RFR rats compared with the controls and PF rats. However, there was no statistical difference in percent visceral fat mass among the experimental groups. Lipoprotein lipase (LPL) mRNA levels of RFR rats were significantly increased in RT-WAT compared with the controls and PF rats. These data indicated that leptin was up-regulated in response to chronic repeated fasting and refeeding cycles without a concomitant increase in adiposity, and the augmented leptin levels were associated with an increase in POMC gene expression, reduced food intake, and diminished body weight gain.     

Environment modulates naloxone's suppressive effect on feeding in diabetic and non-diabetic rats

We evaluated the effect of environment on naloxone-induced suppression of feeding in streptozotocin rats and sham injected controls. Naloxone was administered to animals fasted for 24 hours and food intake was measured at 30, 60 and 120 minutes. Diabetic rats, in their home cages, were insensitive to naloxone's suppressive effect for the first 30 minutes and the 5 mg/kg dose suppressed feeding only at 120 minutes. In control rats, feeding was suppressed at 1 and 5 mg/kg naloxone during the first 30 minutes. In contrast, when animals were placed in novel plastic cages, control animals were insensitive to naloxone at all time points at doses as high as 5 mg/kg. In novel cages, diabetic rats responded to doses of 1 and 5 mg/kg during the first 30 minute period by lowering food intake. It should also be noted that basal food intake was suppressed (40-53%) when animals were placed in novel cages. These data suggest that stress of a novel environment alters the neuroregulatory system involved in inducing feeding. Lack of response of normal rats to naloxone's suppressive effect in a novel environment suggests that (1) a non-opioid feeding system operates under these conditions, or (2) opioid receptors are occupied as a result of the release of endogenous opioids due to stress. The opposite result observed in the diabetics indicates that glucose has a modulating effect on opioid effects.     

Nutritional status modulates behavioural and olfactory bulb Fos responses to isoamyl acetate or food odour in rats: roles of orexins and leptin

Food odours are major determinants for food choice, and their detection depends on nutritional status. The effects of different odour stimuli on both behavioural responses (locomotor activity and sniffing) and Fos induction in olfactory bulbs (OB) were studied in satiated or 48-h fasted rats. We focused on two odour stimuli: isoamyl acetate (ISO), as a neutral stimulus either unknown or familiar, and food pellet odour, that were presented to quiet rats during the light phase of the day. We found significant effects of nutritional status and odour stimulus on both behavioural and OB responses. The locomotor activity induced by odour stimuli was always more marked in fasted than in satiated rats, and food odour induced increased sniffing activity only in fasted rats. Fos expression was quantified in periglomerular, mitral and granular OB cell layers. As a new odour, ISO induced a significant increase in Fos expression in all OB layers, similar in fasted and satiated rats. Significant OB responses to familiar odours were only observed in fasted rats. Among the numerous peptides shown to vary after 48 h of fasting, we focused on orexins (for which immunoreactive fibres are present in the OB) and leptin, as a peripheral hormone linked to adiposity, and tested their effects of food odour. The administration of orexin A in satiated animals partially mimicked fasting, since food odour increased OB Fos responses, but did not induce sniffing. The treatment of fasted animals with either an orexin receptors antagonist (ACT-078573) or leptin significantly decreased both locomotor activity, time spent sniffing food odour and OB Fos induction in all cell layers, thus mimicking a satiated status. We conclude that orexins and leptin are some of the factors that can modify behavioural and OB Fos responses to a familiar food odour.     

Effect of deprivation and time of refeeding on food intake.

The amount of food eaten in a two hour trial by male Sprague Dawley rats was recorded after periods of food deprivation up to 42 hr in length. Rats ate 50-78% more when refed during the dark phase than when refed during the light phase. This occurred even when light fed animals were fasted for longer periods than the dark fed animals. Rats eat in a rhythmic pattern after deprivation. These data are in good agreement with data previously reported and extend it by increasing the number of observations, increasing the length of deprivation, and comparing different age groups.     

Changes in insulin, glucose and GH concentrations in fed chickens

The concentrations of insulin, glucose and growth hormone were examined in chickens during the fed and fasted states. In broiler chickens between 5 and 7 weeks of age, blood samples were drawn at intervals which reflected fed (-4 hr), fasted (+0 min) and post meal states (+15 min, immediately after a 15 min meal (and +30 min). Plasma was assayed using a chicken insulin standard in a heterologous RIA. Overall insulin averages, reflecting averaged values for 10 birds/day and 5 replications revealed a decrease with fasting and an increase post-meal. Insulin levels returned to pre-fasted concentrations within 15 min of meal termination. Changes in glucose concentrations correlated with those of insulin with the exception of the +30 min period. When insulin levels were observed in chickens where no food was consumed, insulin levels at +0 and +15 min were not different. No difference in GH concentration occurred at -4 hr, +0 or +15 min but the +30 min value increased (p less than 0.05).     

2-deoxy-D-glucose inhibits food intake in rats after ventromedial hypothalamic lesions

Changes in food induced by 2 deoxy-D-glucose (2 DG) have been investigated in newly lesioned rats during the two parts of the diurnal cycle. In a first experiment rats were injected with saline or 2 DG (250, 500, 750 mg/kg) at the beginning of the light or the dark period. In a second experiment rats were injected with saline or 2 DG (250 mg/kg) in the middle of the two periods after 0, 2, 4 or 6 hr of fasting. Results show that 2 DG exerts an inhibitory effect on food intake at night, as it does in intact rats, under ad lib conditions or after a short deprivation time. The stimulating effects of 2 DG on diurnal food intake observed in intact rats is not replicated in VMH rats. On the contrary an inhibition of intake follows a short food deprivation. The data suggest that 2 DG stimulates food intake only under metabolic and feeding conditions characteristic of the diurnal phase in intact rats. Since lipogenesis and hyperphagia are observed 24 hr a day in VMH animals, only inhibition could follow 2 DG.     

The effect of serotonergic system on nociceptin/orphanin FQ induced food intake in chicken

The present study was designed to examine the effects of intracerebroventricular injection of para-chlorophenylalanine (PCPA) (cerebral serotonin depletive), fluoxetine (selective serotonin reuptake inhibitor), 8-OH-DPAT (5-HT_1A autoreceptor agonist) and SB 242084 (5-HT_2c receptor antagonist) on nociceptin/orphanin FQ (N/OFQ) induced feeding response in chickens. A guide cannula was surgically implanted into the lateral ventricle of chickens. Before the experiments, 3-h fasting periods had been given to all experimental birds. In experiment 1, chickens were injected with PCPA (1.5 μg) followed by an N/OFQ injection (16 nmol) intracerebroventricularly. In experiment 2, birds received fluoxetine (10 μg) prior to the injection of N/OFQ. In experiment 3, chickens were administered with N/OFQ after the 8-OH-DPAT administration (15.25 nmol). In experiment 4, birds were injected with SB 242084 (1.5 μg) followed by an N/OFQ injection. Cumulative food intake was measured at 3 h post injection. The results of this study show that N/OFQ increases food intake in broiler cockerels (P < 0.05) and that this effect is amplified by pretreatment with PCPA and SB 242084 in an additive manner (P < 0.05). The effect of N/OFQ is not changed by pretreatment with 8-OH-DPAT (P > 0.05). Furthermore, the stimulatory effect of N/OFQ on food intake was significantly attenuated by pretreatment with fluoxetine. These results suggest that N/OFQ induced hyperphagia is mediated by serotonergic mechanisms, and possibly imply an interaction between N/OFQ and the serotonergic system (via 5-HT_2C receptors) on food intake in chickens.     

Effects of the 5-HT1A receptor agonist 8-OH-DPAT on operant food intake in food-deprived pigs.

The effects of the 5-HT1A agonist 8-hydroxy-2 (di-n-propylamino)tetralin (8-OH-DPAT) were investigated on operant food intake in food-deprived pigs. In Experiment 1, 8-OH-DPAT (5-20 microg/kg) administered intravenously (i.v.) 15 min prior to the occurrence of feeding produced a dose-related decrease in operant food intake in pigs that had been fasted overnight. The effects were mainly apparent during the first 30 min after the start of the feeding period. In Experiment 2, 8-OH-DPAT (25 and 50 microg/kg, i.v.) administered 60 min prior to the occurrence of feeding in pigs that were fasted overnight also produced significant decreases in food intake. The effects were mainly apparent during the first 30-40 min after the start of the feeding period. In Experiment 3, 8-OH-DPAT (20 microg/kg, i.v.) significantly increased operant feeding in satiated pigs during the first 30 min after administration. These results show that 8-OH-DPAT has complex effects on feeding behaviour in pigs, increasing operant food intake in satiated pigs, while producing a reduction in food intake in food-deprived animals.     

The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema

Ghrelin is mainly secreted during fasting. While an orexigenic effect of peripherally injected ghrelin has been reported, reproducing this effect has often proven difficult. Here, we hypothesized that ghrelin's effect to increase food intake may depend on the experimental conditions (e.g., age of animals). We therefore investigated the effect of an IP ghrelin injection (100 microg/kg) on food intake in rats of different age and at different times during the light-dark cycle, i.e. with different levels of baseline food intake. Ghrelin injected at dark onset in ad libitum fed young rats (body weight [BW] 92 g) slightly increased feeding while no such effect was observed in 12 h food deprived rats (BW 150 g). In the middle of the light phase, ghrelin significantly increased feeding up to 2 h after injection in ad libitum fed rats (BW 130 g; food intake 1 h after injection: NaCl 0.4 +/- 0.2 g versus ghrelin 1.2 +/- 0.3 g [p < 0.05]). In various subsequent experiments, older rats (BW 300-490 g) tested under the same conditions did not respond to a single ghrelin injection. However repeated ghrelin injection (15 microg/kg/day once daily at light onset) over 10 days significantly increased food intake in rats (BW 400-460 g) starting from day 4 of the experiment (24 h food intake: NaCl approx. 19.5 g, ghrelin 22.5 g). Interestingly, the latter effect was completely abolished in rats lesioned in the area postrema (AP). Cumulative food intake was also increased in SHAM but not in AP-X animals (e.g., after 7 days: SHAM/NaCl 135.1 +/- 5.3 g versus SHAM/ghrelin 149.7 +/- 3.5 g [p < 0.05], AP-X/NaCl 127.2 +/- 16.4 versus AP-X/ghrelin 127.9 +/- 5.3). We conclude that ghrelin's effect to increase food intake can best be demonstrated when basal food intake is low. Ghrelin increases feeding mainly in young, fast growing animals. Ghrelin may therefore link the high energy needs to body growth in young individuals. In older animals, peripheral ghrelin increased feeding when injected repeatedly over several days. At least under these conditions, ghrelin's effect was mediated by the AP/NTS region. Using repeated administration, ghrelin might be an interesting tool to increase feeding in patients suffering from wasting diseases such as cancer anorexia.     

Effect of Terbutaline, a β2-adrenergic Receptor Stimulating Compound, on Cutaneous Responses to Histamine, Allergen, Compound 48/80, and Trypsin

The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.     

Calcitonin gene-related peptide promotes transient radiocalcium uptake into chick bone in vivo

We have examined the in vivo effects in chicks of intravenously injected chicken (c-) and rat (r-) calcitonin gene-related peptides (CGRP) on uptake into bone of a simultaneously administered 45Ca label. Both peptides caused transient (10 min) increases in 45Ca uptake into a variety of bone types. In dose-response experiments at 10 min, CGRP doses of 0.26-1.04 nmol/100 g body wt were found to give maximal responses. These were well developed in chicks fasted for 22 h but absent in those which were continuously fed. This contrasts with the hypercalcaemic effect of CGRP which is apparent in fed rather than fasted chicks.     

Effects of feeding, fasting and refeeding on growth hormone and insulin in obese pigs

This study has indicated that temporal patterns of plasma GH changes were similar in lean and obese pigs with one to two secretory spikes occurring during a 6-hour period. Fasting caused increased GH in both pig strains; however, obese pigs, compared to lean, had lower GH during feeding and fasting. This depressed plasma GH of obese pigs may not be due entirely to impaired pituitary function since refeeding caused increased GH to levels similar to lean pigs. Insulin response per unit of feed intake was greater in obese pigs compared to lean. Together with higher insulin to glucose ratios, these results indicate hyperinsulinemia in the obese pigs. Overall, hormone and glucose responses were influenced by the nutritive status--fed, fasted or refed. Therefore consideration of feeding schedule was important in assessment of hormonal differences between the lean and obese pigs.