Setsuo Kobayashi

The significance of decreased ambulatory activity during the generation by long-term observation of obesity in ovariectomized rats.

We attempted to determine the significance of ambulatory activity as a cause of overweight in ovariectomized rats. Drinking and ambulation were measured continuously and directly for periods up to 12 months in special apparatus developed at Gunma University. In older rats, ambulatory activity decreased much more in the ovariectomy group than in the control group. There was no difference in food intake between the ovariectomized and the control group. After 2 months, the ovariectomy group increased body weight more than the control group despite no difference in food intake. The decrease in ambulatory activity was consistent in the ovariectomy group, regardless of any differences in age and body weight. These results indicate that decrease of energy expenditure by gradual decrease in ambulatory activity may be an important factor as a cause of overweight in ovariectomized, obese rats.

Inhibitory effects of various drugs on dual asthmatic responses in wheat flour-sensitive subjects

In order to investigate the mechanism of late asthmatic response (LAR), inhibitory effects of various drugs for LAR were examined in two wheat flour-sensitive asthmatic subjects who showed immediate and late responses in the allergen provocation test and skin test. Antihistamines did not inhibit the LAR but totally or partially inhibited the immediate response. By contrast, corticosteroids inhibited the LAR but not the immediate response. Disodium cromoglycate inhibited both responses. Diethyl carbamazine citrate, an inhibitor of release of SRS-A, seemed to shorten the duration of the LAR, although it has no effect on the immediate response and/or on the severity of the LAR. Indomethacin and acetyl salicylate, which inhibit prostaglandin synthesis, had no significant effects on either the immediate or the LAR.

Serum prostaglandin levels in asthmatic patients

Levels of serum prostaglandins E and F were measured by radioimmunoassay in 40 asthmatic patients and healthy subjects. Levels of both prostaglandins--E and F--were significantly higher in asthmatic patients than in normal control subjects. The prostaglandin F/prostaglandin E ratio was significantly higher in asthmatic patients than in normal control subjects.

Effects of peripheral administration of recombinant human Interleukin-1 beta on feeding behavior of the rat

This study was undertaken to investigate the changes in feeding behavior, including ambulatory activity, induced by a single injection of Interleukin-1 beta (IL-1) (2 micrograms/rat) at 18:00, just before the dark phase. For this purpose, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. A significant decrease in food intake was observed for 12 hours after treatment with IL-1. Peripheral administration of IL-1 also produced a marked decrease in ambulatory activity within 3 hours which continued for 6 hours. In addition, IL-1 produced a marked decrease in drinking behavior during the first 6 hours. We reported here the changes in consummatory and ambulatory behavior of rats after acute administration of IL-1. The sickness which IL-1 produced may, at least in part, contribute to these phenomena, although precise mechanisms are still unknown.

Role of the hypothalamic TRH in the regulation of its own receptors in rat anterior pituitaries.

We explored whether endogenous TRH in the hypothalamus produced a potential change in its receptors in the rat anterior pituitary. Thyroidectomy caused a progressive increase in the pituitary TRH binding with a concomitant increase in the blood TSH level. Injection of T4 prevented the increase in the pituitary TRH binding and the blood TSH level after thyroidectomy. The hypothalamic deafferentation and electrolytic lesions in the hypothalamic paraventricular nuclei led to a significant reduction in both the content of TRH in the hypothalamic median eminence and the blood TSH level, but they affected neither the number nor affinity constant of the pituitary TRH receptors in thyroidectomized rats. The present data provide evidence that TRH receptors in the anterior pituitary are profoundly regulated by thyroid hormones, but not significantly by TRH in the hypothalamus in the rat.

Intraventricular Administration of Cyclo(His-Pro), a Metabolite of Thyrotropin-Releasing Hormone (TRH), Decreases Water Intake in the Rat

Abstract We explored the effect of cyclo(His-Pro) on drinking in water-deprived rats. Intraventricular administration of cyclo(His-Pro) significantly reduced water intake in these rats in a dose-dependent fashion (3 × 10−10-3 × 10−8 mole), whereas its intrapentoneal injection did not cause any effect on water intake. The inhibitory potency of cyclo(His-Pro) was found to be similar to that of thyrotropin-releasing hormone (TRH), but cyclo(His-Pro) did not significantly interfere with TRH binding in the rat brain. The data indicate that cyclo(His-Pro) action was not mediated through the TRH counterpart. These results suggest that cyclo(His-Pro) may play a potential role in the regulation of water intake in the rat brain.

Abnormal feeding behavior and insulin replacement in STZ-induced diabetic rats.

The present studies were undertaken to investigate whether or not decreased ambulatory activity, including abnormal feeding behavior in diabetic rats, will be simultaneously normalized by insulin administration. To do this, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. In this study, 3 U NPH insulin were administered at 1800, just before the dark phase, and 2 U were administered at 0600, just before the light phase. With these insulin doses, we found that 5 weeks were needed to normalize ambulatory activity, 4 weeks were necessary for food intake, 6 weeks for drinking and 2 weeks for body weight. Since ambulatory activity is reported to be related to changes in dopamine turnover, further studies are in progress to determine whether or not dopamine turnover is normalized when there is no difference in ambulatory activity due to insulin replacement.

Effects of Recombinant Human Interleukins on Food Intake of Previously Food-Deprived Rats

Abstract The effects of intracerebroventricular injection of recombinant human interleukin 1β (rhIL-1β), 1α (rhIL-1α), and 2 (rhIL-2) on feeding behavior were examined in previously food-deprived rats for 18 hr. At doses of 2–17 ng/rat, rhIL-1β significantly reduced food intake in a dose-dependent manner and the feeding suppression continued about 4 hr later. Only 17 ng/rat rhIL-1β reduced body weight gain for 8 hr after the injection. However, rhIL-1α at dose of 17 ng/rat did not show any significant change of food intake and body weight gain during the whole observation period. At both doses of 8 and 40 ng/rat, rhIL-2 also failed to suppress overfeeding after food deprivation. In adrenalectomized rats, feeding suppression by rhIL-1β appeared at the 1- to 2-hr time period. The present studies suggest that rhIL-1β may be, at least in part, involved in feeding suppression on various inflammatory processes and that adrenal hormones may not play an important role in the induction of feeding suppression by rhIL-1β.

Naturally occurring aliphatic polyamines-induced histamine release from rat peritoneal mast cells

Rat peritoneal mast cells were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1‐10mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose‐dependent manner. The effect of 10 mM spermine and spermidine was as much as that of 0.5 μg/ml compound 48/80. The histamine release from the cells incubated with each polyamine was rapid and the amount of histamine release into the supernatant solutions reached a maximum at 1 min with the incubations. 0.1 mM spermine, which in itself could not cause a significant histamine release, showed a tendency to enhance anti‐IgE‐induced histamine release from the mast cells.

The relationship between interdigestive gallbladder and gastroduodenal motility in man

SummaryThe relationship between interdigestive gallbladder and gastroduodenal motilty simultaneously with the behavior of plasma motilin and CCK levels in 20 subjects was investigated. We used an infusion catheter method for the measurement of gastroduodenal motility, and real-time ultrasonography for the measurement of gallbladder size. In gastric phase II, the gallbladder contracted with extension of the major axis and shrinking of the minor axis, with its minimum volume being 84% of the volume in phase I. The gallbladder then filled rapidly assuming a sphere-like shape with extension of the minor axis and shrinking of the major axis in gastric phase I. This motility was recognized only during the gastrointestinal interdigestive migrating complex (GI-IMC) cycle, originating in the stomach, and was associated with an increase of motilin levels, it was not seen before or after the intestinal IMC (I-IMC), which originated in the duodenum without contraction of the stomach or an increase of motilin levels. Furthermore no apparent relationship was recognized between CCK and gastric or gallbaldder motility. Our findings suggest that gallbladder motility in the interdigestive period has a close relationship with gastroduodenal motility and is related to the appearance of the GI-IMC.