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K Hashizume

Publications and source records attributed to K Hashizume.

28 records · Page 2Linked to original sources
PubMed1976

[Studies on the thyrotropin receptor in the thyroid: positive cooperativity of Concanavalin A binding and its biphasic effects on thyroid activation induced by thyrotropin (author's transl)].

Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by the thyroid stimulators in mouse thyroid tissues. Con A was found to have the biphasic stimulatory and inhibitory effects of thyrotropin (TSH)-induced cyclic AMP formation and endocytosis, a step in thyroid hormone secretion, in mouse thyroid tissues. Low concentrations of Con A potentiated TSH-stimulated cyclic AMP formation and endocytosis. In contrast, high concentrations of Con A markedly inhibited TSH stimulations. These effects were reversed by the addition of methyl-alpha-D-glucoside to the second preincubation medium (without Con A) prior to TSH. A high concentration of Con A alone did not depress the basal levels of cyclic AMP or basal glucose oxidation in thyroid tissues. A high concentration of Con A also inhibited cyclic AMP formation induced by prostaglandin E2 and the long-acting thyroid stimulator (LATS). Binding of 125I-labeled Con A to thyroid tissues increased with time up to 75 min and was very slowly reversible after attainment of equilibrium. Binding was directly proportional to tissue weight. Scatchard plot analysis on the binding of 125I-labeled Con A to thyroid tissues indicated a positive cooperativity which seemed to be well correlated to the biphasic effects.

Animals↗
PubMed1976

[The histaminergic mechanisms in the regulation of prolactin secretion in urethan-anesthetized rats (author's transl)].

In an attempt to detect the existence of histaminergic mechanisms in the regulation of prolactin secretion in rats, the effects of histidine and histamine-receptor antagonists (chlorpheniramine and metiamide) on plasma prolactin levels in urethan-anesthetized rats were investigated in relation to other aminergic mechanisms. Chlorpheniramine was used as an H1-receptor antagonist and metiamide as an H2-receptor antagonist. Wistar male rats were used under urethan anesthesia and blood was obtained by cardiac puncture. Rat plasma prolactin was measured by radioimmunoassay. As already reported, L-DOPA and diethyldithiocarbamate markedly decreased plasma prolactin levels in rats. Dihydroxyphenylserine increased prolactin levels. Brocresine phosphate, a histidine decarboxylase inhibitor, markedly stimulated prolactin secretion in urethan-anesthetized rats. This stimulation was not blocked by pretreatment with histidine or L-DOPA. Histidine alone did not affect plasma levels of prolactin or methyldopamine-induced increase in plasma prolactin levels. On the other hand, histidine significantly stimulated prolactin secretion in chlorpheniramine-treated rats. In contrast, histidine depressed plasma prolactin levels in metiamide-treated rats. These findings indicate that a dopaminergic component is inhibitory and a noradrenergic one is stimulatory in prolactin secretion in rats and further that there exist the histaminergic mechanisms, relatively independent from other aminergic mechanisms, which might also play an important role in the regulation of prolactin secretion in rats. Furthermore, it is suggested that H1-receptor is stimulatory and H2-receptor is inhibitory in prolactin secretion in rats.

Animals↗
PubMed1976

Effects of drugs that modify brain biogenic amine concentrations on thyroid activation induced by exposure to cold.

L-Dihydroxphenylalanine (L-DOPA) significantly inhibited intrathyroidal colloid droplet formation induced by exposure to cold in the rat. Diethyldithiocarbamate (DDC) also inhibited colloid droplet formation in response to cold. The combined administration of L-DOPA and DDC produced an additive inhibition of the thyroidal endocytotic response to exposure to cold. Pretreatment with chlorpromazine (CPZ) ameliorated the inhibitory effect of L-DOPA. DL-alpha-methyl-p-tyrosine (alpha-MT) also signficantly depressed the thyroidal response. Inhibition of colloid droplet formation induced by alpha-MT was not altered by the administration of DL-dihydroxyphenylserine (DL-DOPS). On the other hand, treatment of the alpha-MT-treated rats with L-DOPA to normalize dopamine synthesis resulted in a dramatic recovery from the inhibition. Blockade of serotonin biosynthesis with p-chlorophenylalanine (p-CPA) failed to produce a significant inhibition of colloid droplet formation. However, 5-hydroxytryptophan (5-HTP) markedly inhibited the thyroidal response to cold. Brocresine phosphate (BP) was another inhibitor of the thyroidal endocytotic response to exposure to cold. Oxotremorine also markedly depressed the thyroidal response to cold. Since these drugs did not interfere with pituitary thyroid responsiveness to exogenous thyrotropin-releasing hormone (TRH), it seems that the throidal endocytotic response to exposure to cold as a reflection of TSH secretion was directly influenced by alterations of brain biogenic amine concentrations or turnover rates.

5-Hydroxytryptophan↗
PubMed1976

The inhibitory effect of acute administration of excess iodide on the formation of adenosine 3', 5'-monophosphate induced by thyrotropin in mouse thyroid lobes.

In a previous paper, we demonstrated that an inhibitory action of excess iodide on thyrotropin-induced thyroid hormone secretion occurs at a site subsequent to the generation of cyclic AMP. In the present study, however, we have found that thyroidal cyclic AMP formation induced by thyrotropin in vitro was markedly inhibited by the acute administration of excess iodide to mice fed a low iodine diet. In contrast, excess iodide failed to produce inhibition in animals fed a regular diet. In vitro stimulation by long-acting thyroid stimulator (LATS), prostaglandin E2, and 4-methylhistamine of cyclic AMP formation in mouse thyroid lobes was also significantly inhibited by the acute in vivo administration of excess iodide. The inhibition was completely relieved by the administration of methimazole prior to excess iodide. Furthermore, it has been shown that thyroid adenylate cyclase activity induced by thyrotropin was markedly depressed by excess iodide under similar experimental conditions. Therefore, it is suggested that one of the inhibitory actions of excess iodide is on the adenylate cyclase-cyclic AMP system and further, that iodide can elicit its inhibitory action after its conversion to some form of organic iodine.

Adenylyl Cyclases↗
PubMed1976

Effects of biogenic amines on the formation of adenosine 3', 5'-monophosphate in human thyroid slices.

The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibitied by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology.

Biogenic Amines↗
PubMed1975

The role of the pentose phosphate shunt in thyrotropin-induced thyroid hormone secretion: in vivo and vitro studies with 6-aminonicotinamide in mouse thyroids.

The possible role of the pentose phosphate shunt in thyroid hormone secretion was investigated in vivo and in vitro with mouse thyroid glands. Thyroidal endocytosis in response to TSH, a step of thyroid hormone secretion, was evaluated for its dependency upon the pentose phosphate shunt by using 6-aminonicotinamide (6-AN), an antimetabolite in the synthesis of pyridine nucleotides. Formation of 14CO2 from glucose labeled either in the C-1 or C-6 position was studied to estimate the pentose phosphate shunt activity. A dose of 6-AN markedly reduced oxidation of [1-14C]glucose but did not affect that of [6-14C]glucose induced by TSH. Concomitantly there was a marked decrease in thyroidal endocytotic response to TSH. These inhibitions by 6-AN were completely abolished by the pretreatment with nicotinamide. Methylene blue, which oxidizes NADPH and thus stimulates activity of the pentose shunt, significantly depressed thyroidal endocytosis in response to TSH in vitro. These inhibitions of colloid droplet formation by 6-AN or methylene blue were not manifested against dibutyryl cyclic AMP stimulation. Furthermore, a dose of 6-AN, which seems to inhibit only the pentose phosphate shunt, markedly depressed TSH-induced formation of cyclic amp. These findings suggest that the pentose phosphate shunt might play an important role in triggering TSH stimulation of thyroid hormone secretion by supplying NADPH, and further, that NADPH dependency in thyroid hormone secretion is at a site prior to the generation of cyclic AMP.

6-Aminonicotinamide↗