Toshikiyo Koh

Effects of food deprivation and high fat diet on opioid receptor binding in rat brain.

The effect of food deprivation for 72 h or a high fat diet on [3H]naloxone binding in the discrete brain regions of male lean Zucker rats was studied. In the midbrain, both treatments increased Bmax for the high-affinity site with no change in Kd. In the cortex, the high fat diet increased Bmax for the high-affinity site. These results suggest that dietary manipulations could produce significant changes in the endogenous opioid system.

Perception of hunger and satiety induced by 2‐deoxy‐D‐glucose in anorexia nervosa and bulimia nervosa

The effect of intracellular glucopenia induced by 2-deoxy-D-glucose (2-DG) on changes in hunger ratings, blood glucose, plasms cortisol, and prolactin levels were examined in six female patients with primary anorexia nervosa, three patients with bulimia nervosa, and six age-and sex-matched volunteers. In the normal subjects, hunger ratings obtained by the linear visual analog technique increased significantly at 60 minutes after 2-DG infusion and remained elevated. In Patients with anorexia nervosa, however, hunger ratins paradoxically decreased significantly at 90 minutes. In normal subjects, the ingestion of a 20-minute lunch relieved hunger, but neither the anorexic patients nor bulimic patients felt satiety even after food intake. These results suggest that the perception of hunger induced by 2-DG in anorexia nervosa and that of satiety in anorexia nervosa and bulimia nervosa are disturbed.

Effect of food deprivation on opioid receptor binding in the brain of lean and fatty Zucker rats.

The effect of food deprivation on opioid receptor binding was studied in 6 brain regions of lean and fatty Zucker rats; using [3H]dynorphin A. There was no significant difference between lean and fatty rats fed ad libitum in binding parameters for any regions studied. Food deprivation increased Bmax and/or Kd for cortex, midbrain and striatum of lean rats, and the former two regions of fatty rats. These results suggest that food deprivation may influence opioid receptor binding in lean and fatty Zucker rats.

Taste function in patients with anorexia nervosa and bulimia nervosa

The sensitivity to sucrose, sodium hydrochloride, tartrate, and quinine was examined by a filter paper disc method in patients with anorexia nervosa and with bulimia nervosa. There were 20 of the 23 anorexia patients and 11 of the 13 bulimic patients who showed hypogeusia. There were 12 of the 23 anorexia patients and 8 of the 13 bulimia patients who showed dysgeusia. Seven anorexia patients were restudied when the treatments produced a weight gain to more than 85% of normal body weight. Taste function had improved substantially in all but still was subnormal. Serum zinc, iron, and triiodothyronine levels in these patients were depressed; however, none of these levels correlated with the taste recognition scores or dysgeusia scores. In conclusion, patients with anorexia nervosa and bulimia nervosa showed hypogeusia and/or dysgeusia, although the etiology of the taste dysfunction in these patients remains to be determined. These findings should be considered in the implications for treating these patients.

Serotonin involvement in the inhibition of luteinizing hormone (LH) release during immobilization in castrated male rats

The involvement of serotonin in mediating the inhibitory effect of immobilization stress on LH secretion in castrated male rats was examined by employing p-chlorophenylalanine (PCPA, 320 mg/kg, ip), an inhibitor of serotonin synthesis, and 5,6-dihydroxytryptamine (5,6-DHT, 50 micrograms, icv), a drug toxic to the indoleaminergic system. Immobilization stress suppressed pulsatile LH release and decreased mean plasma LH levels. Pretreatment with PCPA or 5,6-DHT apparently eliminated the inhibitory effect of immobilization stress on LH release. These results suggest the possible involvement of a serotoninergic mechanism in mediating the suppression of LH release induced by immobilization stress in castrated male rats.

Thyrotoxic graves' disease with normal thyroidal technetium-99m pertechnetate uptake

We saw 24 thyrotoxic Graves’ patients with normal thyroidal uptake of technetium-99m pertechnetate (99mTc) out of 201 untreated thyrotoxic Graves’ patients seen over 4 years. The clinical and laboratory findings for these patients were studied and analysed.Thyroid uptake and scintigraphic examinations by means of99mTc, TBII and TSab activity measurement clearly distinguished these patients from other thyrotoxic disorders (destruction-induced thyrotoxicosis and autonomously functioning thyroid lesions). Different from other disorders, these patients had not lower but normal thyroid uptake and also showed diffuse and discrete trapping into the enlarged glands.These patients had significantly smaller goiters, a lower serum thyroid hormone level, and lower TBII and TSab activity, when compared with other high99mTc uptake groups with Graves’ disease, and their condition could be easily controlled with small amounts of antithyroid drugs.Our study indicates that thyrotoxic Graves’ disease with normal99mTc uptake exists and99mTc uptake study and TBII activity measurement is very useful for the diagnosis. The normal99mTc uptake thyrotoxic Graves’ patient might be early stage patients with general Graves’ disease and their early discrimination from general Graves’ patients is very advantageous for treatment and prognosis.

PLASMA DISAPPEARANCE OF OVINE CORTICOTROPHIN‐RELEASING FACTOR IN MAN

Disappearance of immunoreactive ovine corticotrophin‐releasing factor (IR‐oCRF) from plasma after a single intravenous injection of ovine corticotrophinreleasing factor (oCRF) was studied in man in the morning and evening. Synthetic oCRF (80 μg) was injected intravenously to four normal male volunteers at 0900 h or at 2200 h. Blood samples were drawn before and 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after the oCRF injection. Plasma IR‐oCRF was measured by a specific radioimmunoassay for OCRF. Plasma concentrations of IR‐oCRF after oCRF injections in the morning and in the evening did not differ significantly (P>0·05). Disappearance of IR‐oCRF was modelled with a two‐exponent function by using a non‐linear least squares computer program. The metabolic clearance rate, the apparent initial volume of distribution, the plasma half‐life for the fast component and that for the slow component calculated from all eight tests in the morning and evening were 1·49·0±05 ml/min·kg, 44·4±1·7 ml/kg, 6·8±0·7 min and 46·2±2·3 min (mean ± SEM), respectively. This relatively long half‐life may be responsible for the prolonged biological effect of oCRF administered intravenously. There were no significant differences between parameters of IR‐oCRF disappearance curves in the morning and those in the evening (P>0·05).

Evidence for noradrenergic involvement in naloxone-induced stimulation of luteinizing hormone release in prepubertal female rats

The effects of phenoxybenzamine an alpha-adrenergic blocker, propranolol a beta-adrenergic blocker, and diethyldithiocarbamate a noradrenaline synthesis inhibitor, on the LH increase induced by naloxone an opiate antagonist, was investigated in 25 day old female rats. Pretreatment with phenoxybenzamine or diethyldithiocarbamate suppressed the LH increase induced by naloxone, whereas pretreatment with propranolol had no significant effects on the naloxone-induced LH release. These results suggest that naloxone-induced increase in LH release is mediated via a noradrenergic mechanism.

Effect of food deprivation on regional brain glucose utilization in lean and fatty Zucker rats

Regional brain glucose utilization was investigated in lean and fatty Zucker rats when feeding status was changed. Ad-lib-fed fat rats exhibited lower glucose utilization in the central amygdala than ad-lib-fed lean rats. Food deprivation for 72 h enhanced glucose utilization in the ventromedial hypothalamus, lateral hypothalamic area of both phenotypes, hippocampus of fat rats, mammillary body and ventral tegmental area of leans. These results suggest association of the central amygdala with the development of genetic obesity and of the latter 5 areas with hunger-motivated behaviors.

Serotonin involvement in the inhibition of luteinizing hormone (LH) release induced by prostaglandin D2 (PGD2) in castrated male rats

p-Chlorophenylalanine (PCPA, 320 mg/kg i.p.), an inhibitor of serotonin (5-HT) synthesis, and 5,6-dihydroxy-tryptamine (5,6-DHT, 50 micrograms i.c.v.), a drug toxic to the indoleaminergic system were used to test the involvement of 5-HT in the mediation of the inhibitory effect of prostaglandin D2 (PGD2) on luteinizing hormone (LH) release in castrated male rats. The i.c.v. administration of PGD2 suppressed the episodic LH release characteristic of castrated rats and decreased mean plasma LH levels and mean LH pulse amplitude significantly. Pretreatment with PCPA or 5,6-DHT apparently eliminated the inhibitory effect of PGD2 on LH secretion. These results suggest the possible involvement of a serotonergic mechanism in the mediation of the suppression of LH secretion induced by PGD2 in castrated male rats.