Comparative effects of caerulein on food intake and pancreatic secretion in dogs

We compared effects of the CCK analog caerulein on feeding and pancreatic secretion. Nine fasted mongrel dogs with gastric and pancreatic fistulas received scalar doses of caerulein (0, 6.25, 12.5, 25, 50, 100, 200, 400 pmol/kg-hr, each for 30 min). The D50 dose for stimulation of pancreatic secretion was 15 pmol/kg-hr. Effects of intravenous caerulein (0 to 800 pmol/kg-hr; 15 min before and during a 45 min test meal) on food intake were examined in 8 beagles under 4 feeding conditions: 1 meal/day (22 hr fast), 2 meals/day (4 hr fast), 2 meals/day (19 hr fast), and after ad lib access to food followed by a 4 hr fast. The lowest doses that inhibited feeding were: 400 pmol/kg-hr for feeding condition, 200 pmol/kg-hr for and, and 150 pmol/kg-hr for. We conclude: the potency of caerulein for inhibition of food intake is dependent upon feeding condition; these results do not support a role for CCK as a satiety hormone, since the lowest dose of caerulein for inhibition of feeding was 10 times larger than the D50 dose of caerulein for stimulation of pancreatic secretion.     

杭州市高教园区大学生对环境的满意度分析

目的了解高教园区大学生对环境的满意度及需要解决的问题，为高校建设的策划和构建提供必要的参考依据。方法采用多级抽样方法对杭州市高教园区880名大学生进行关于学习、生活、就医、安全保障、交通、人际交往和社会实践环境变化满意度的问卷调查。结果42．7％的大学生对于高教园区的学习环境表示满意。大多数大学生对高教园区的交通环境、社会实践环境和安全保障环境不满意。40．5％的大学生希望尽快改善班车路线少、车次少、价格贵的交通状况。结论高教园区的交通环境迫切需要改善，以满足大学生的学习和生活需求。     

Anorexic action of a new potential neuropeptide Y antagonist [ -Tyr, -Thr]-NPY (27–36) infused into the hypothalamus of the rat

Neuropeptide Y (NPY) produces a vigorous feeding response in several species when it is injected into hypothalamic structures involved in eating behavior. The purpose of this study was to determine whether a unique carboxy terminal fragment of NPY would alter the pattern of eating induced in the rat either by NPY injected into the hypothalamus or by a 24-h period of food deprivation. In this case, two -tyrosine residues and one t.-threonine residue of the NPY_27–36 fragment were transformed to their D-conformation to produce [ -Tyr^27,36, -Thr³²]-NPY (27–36), i.e., D-NPY_27–36. Guide cannulae for microinjection were implanted stereotaxically just dorsal to the paraventricular nucleus (PVN) or ventromedial hypothalamus (VMH) of 24 adult male Sprague-Dawley rats. Following postoperative recovery, a microinjection of artificial CSF or 1.1 jig or 3.3 μg of a peptide was made directly into the PVN or VMH as follows; native NPY; D-NPY_27–36; or [L-Tyr^27,36 L-Thr³²]-NPY (27–36), i.e., L-NPY_27–36. Food intakes were measured at intervals of 0.25, 0.5, 1.1, 2.0, 4.0, and 24 h. When D-NPY_27–36 was microinjected at NPY reactive sites in the PVN or VMH of the rat 15 min before a similar microinjection of NPY, the intense eating response induced by the peptide was reduced significantly. Not only was the effect dose dependent, but D-NPY_27–36 also augmented the latency to feed. A mixture of the two doses of NPY and DNPY_27–36 injected at the same hypothalamic loci did not attenuate the intake of food but tended to enhance the feeding response in the rats. After the rats were deprived of food for 24 h, D-NPY_27–36 microinjected in the same hypothalamic sites similarly caused a dose-dependent suppression of normal feeding behavior. However, the CSF control vehicle and L-NPY_27–36 microinjected in the PVN or VMH were without effect on the pattern of eating. Further, D-NPY_27–38 injected in the same hypothalamic sites affected neither body temperature nor water intakes of the rats significantly. These results demonstrate that the D substitution of this C-fragment of the NPY molecule, i.e., D-NPY_27–36, serves to inhibit feeding evoked in the rat by hypothalamic NPY as well as the natural eating response to food deprivation. Thus, the D-NPY_27–36 molecule may act as an antagonist at one or more subtypes of the NPY receptor in the brain of the rat.     

Increased food intake in satiated rats induced by the 5-HT antagonists methysergide,metergoline and ritanserin

Two series of experiments examined whether 5-hydroxytryptamine (5-HT) antagonists induce feeding in rats. In the first series of experiments separate groups of rats were injected with various doses of methysergide, cyproheptadine, metergoline or ritanserin prior to a 2 h period of access to a wet mash diet which induced vigorous feeding under control conditions. None of the antagonists increased food intake in this paradigm. Rather, at certain doses, methysergide, cyproheptadine and ritanserin induced slight decreases in food intake. Since 5-HT may be involved in controlling satiety, it may be that a more appropriate test of the efficacy of these compounds involves administering them to maximally satiated rats. Consequently, the effects of these drugs were investigated in groups of rats which had fed to satiety immediately prior to drug treatment. In this paradigm methysergide, metergoline and ritanserin, but not cyproheptadine, induced definite increases in food intake. It is suggested that this effect occurs via a dissipation of satiety signals, and that these results further support the hypothesis that 5-HT is involved in controlling satiety. The possibility that these antagonists act on peripheral 5-HT systems is discussed.     

Push-pull perfusion reveals meal-dependent changes in the release of bombesin-like peptides in the rat paraventricular nucleus

Bombesin (BN)-like peptides have been implicated in the regulation of ingestive behavior. The main objective of the present study was to monitor the dynamics of central BN-like peptide release in relationship to spontaneous meal ingestion and termination. Peptide level fluctuations were determined using in vivo push-pull perfusion of the hypothalamic paraventricular nucleus (PVN) and off PVN sites, combined with ex vivo radioimmunoassay. Analysis across all meals revealed significant differences between preprandial, prandial and postprandial extracellular BN-like immunoreactivity (BLI) at the anterior aspect of the PVN, with about a 3-fold diminution during a meal as compared to before or after a meal. Meal-related fluctuations were not detected at more distal hypothalamic sites or at sites within the caudate nucleus. When the analysis was restricted exclusively to the first meal after dark onset, a similar pattern of change in the interstitial levels of PVN BLI was generally observed; levels being higher preprandially as compared to the prandially (albeit by a smaller magnitude), and the termination of the first meal being accompanied by a robust (about 3-fold) increase in BLI. This is the first demonstration of site specific in vivo release of BN-like peptides in relation to feeding status and it further supports the physiological role of this family of peptides in the regulation of food intake.     

Effects of pre-feeding on food-approach latency and food consumption speed in food deprived rats

Deprived rats were trained to receive a major portion of their daily food ration in meal segments of five 45 mg food pellets, presented for 36 sec each at 72 sec intervals. Latency to make oral contact with first pellets did not change over 18 meal segments, while the time to complete the eating of meal segments increased progressively. Pre-feeding with 45 or 90 pellets had little effect on latencies except in the last few trials in the 90-pellet condition. Pre-feeding had a marked effect on time to complete segments, increasing it in proportion to the number of pellets consumed. Thus satiation caused a progressive change in speed of eating, while it caused an all-or-none change in initiation of eating. That is, animals responded to new food pellets with normal latency up to the point when they stopped responding completely. With repeated testing the effects of prefeeding on both speed and latency measures was reduced; the animals ate more steadily, and came to eat every pellet, as familiarity with the situation increased.     

Antagonism of cholecystokinin-like peptides by opioid peptides, morphine or tetrodotoxin

Morphine, beta-endorphin, Met-enkephalin, and Leu-enkephalin antagonized intestinal actions of cholecystokinin octapeptide (CCK-8), caerulein, and pentagastrin in a manner partly suggesting physiologically competitive antagonism. Further, these acidic peptides (CCK-8, caerulein, pentagastrin) were much more sensitive to the actions of opioids than was angiotensin. Tetrodotoxin also caused changes in the concentration-effect curves, but these were different from the shifts due to the opioids and differentiated between CCK-8, caerulein, and pentagastrin. Naloxone did not modify the response to CCK-8 and caerulein, but completely abolished the antagonistic influence of the opioids. The potencies of morphine and the opioid peptides as antagonists of CCK-8, were of nearly the same order of magnitude. This and the presence in gut and brain of both CCK-like and opioid peptides suggests the hypothesis that these two groups of peptides interact on both myenteric and central nervous system receptors, and thus are directly involved in the regulation of both intestinal motility and satiety.     

Effect of liver temperature increase on food intake

Artificial heating of rat liver decreases food intake, while it significantly increases the purposeless chewing during the experiment. The hypothesis is suggested that hepatic thermoreceptors are stimulated by a physiologic increase in liver temperature, which afferent to feeding integrative centers. Liver thermoreceptors rather than chemoreceptors are perhaps regulators of food intake.     

Calmodulin-induced feeding in the satiated cat: Evidence for involvement of calcium and norepinephrine in the brain

The central effect of the Ca++ binding protein, calmodulin (CaM) on spontaneous feeding as well as on core temperature was examined in the satiated cat in which chronically indwelling cannulae were permanently implanted for intracerebroventricular (ICV) infusion. When CaM was injected ICV in doses of 2.5-10.0 micrograms, the intake of food was significantly enhanced in the satiated cat without any notable change in the animal's core temperature. Ca++ ions infused similarly in a solution of 6.25-25.0 mM also augmented the spontaneous ingestion of food, which was accompanied by a concentration-related decline in core temperature. When infused separately, neither CaM in a low dose (1.25 micrograms) nor Ca++ ions (3.0 mM) given ICV altered the intake of food of the satiated cat. However, the simultaneous infusion of CaM and Ca in these concentrations enhanced significantly the amount of food consumed by as much as 60 g. When the same concentration of Ca++ ions was infused ICV simultaneously with 5.0 micrograms troponin C, a Ca++ binding protein of an identical molecular weight, the intake of food was unaltered. Further, the spontaneous feeding induced by CaM could be attenuated either by the central chelation of Ca++ ions by 1.0-1.5 mM EGTA or by 30 micrograms calcineurin, a specific CaM inhibitor, when either was given ICV. Pre-treatment of the cat with ICV phentolamine (50 micrograms) also reduced the CaM-induced feeding response significantly, whereas the similar pre-treatment with ICV propranolol (50 micrograms) or naloxone (100 micrograms) failed to affect CaM-induced feeding behavior.(ABSTRACT TRUNCATED AT 250 WORDS)