Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 91 records · Page 5Linked to original sources

PubMed1994

Histamine-induced bi-directional differentiation of HL-60 cells towards neutrophils and eosinophils.

HL-60 cells, treated under alkaline conditions (pH 7.6) or acidic conditions (pH 7.2) for 2 months, were stimulated with histamine for 7 days. From the morphological examination and cytochemical characterization, it became clear that one of the clones treated in acidic pH differentiated to neutrophils and the other clone treated in alkaline medium differentiated to eosinophils after histamine-stimulation. The growth curve reached a maximum 4 days after stimulation. By means of in situ hybridization, it has been shown that the mRNA of major basic protein increased after histamine treatment only in the eosinophilic subclone, starting 4 days after stimulation. From the present study, it is suggested that when HL-60 cells were cultured under different pH conditions, commitment of lineages to the direction of either eosinophils or neutrophils takes place. Histamine may potently stimulate the further differentiation of both eosinophilic and neutrophilic clones.

Base Sequence↗

PubMed1994

The control of endothelin-1 secretion.

1. The human endothelin-1 (ET-1) gene, which is located on chromosome 6, contains cis-regulatory elements in the 5'-flanking region including the TPA-responsive element, nuclear factor 1 binding element and GATA motif. 2. The expression of preproendothelin-1 (PPET-1) mRNA is regulated by a mechanism involving receptor mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells. 3. Activation of protein kinase C results in the synthesis of c-Jun protein and the rapid dephosphorylation of c-Jun protein. Consequently, the binding activity of c-Jun protein to the TPA-responsive element increases, and this causes the induction of PPET-1 mRNA. 4. The microtubular system seems to play some important roles in ET-1 secretion, especially in the process of transferring the synthesized ET-1 to the cell surface of the endothelial cells. 5. The secretion of ET-1 from endothelial cells is also regulated by intracellular Ca2+ released from the Ca2+ store and by Ca2+-calmodulin complex. The phosphorylation of the myosin light chain, elicited by myosin light chain kinase and activated by Ca2+-calmodulin complex, facilitates the formation of filamentous myosin and actin which probably participate in ET-1 secretion especially in transporting the ET-1-containing vesicles towards the cell membrane in the stimulated endothelial cells. 6. Many cultured cells, other than endothelial cells, also secret ET-1 into the culture medium and this secretion can be stimulated by a variety of agents.

Calcium↗

PubMed1994

Inhibition of tumor necrosis factor-alpha and -beta secretion by lymphokine activated killer cells by transforming growth factor-beta.

Transforming growth factor-beta (TGF-beta) has a variety of immunosuppressive properties. We investigated the effect of TGF-beta secreted by glioblastoma (T98G) cells on the secretion of tumor necrosis factor-alpha and -beta (TNFs) by lymphokine activated killer (LAK) cells stimulated with tumor cells. The supernatant from T98G cells was preincubated with anti-TGF-beta 1 and -beta 2 neutralizing antibodies or untreated, and added to a coculture of LAK and Daudi cells. The neutralizing antibodies were added to LAK/Daudi and LAK culture, and natural human TGF-beta 1 and recombinant human TGF-beta 2 were also added to the LAK/Daudi culture. LAK cells were also cultured with T98G cells, of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, and the neutralizing antibodies were added to the coculture. TNFs activity in the supernatants from LAK/Daudi cultures was examined by a specific bioassay. Addition of the supernatant from T98G cells to LAK/Daudi culture resulted in the inhibition of TNFs secretion by LAK cells. The inhibition was abrogated by the pretreatment of the supernatants with the anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to LAK/Daudi culture inhibited TNFs secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to LAK culture resulted in an increase of TNFs secretion. These results suggest that, if tumor cells have the capacity to convert TGF-beta from a latent to an active form, the active TGF-beta suppresses TNFs secretion by LAK cells stimulated with the tumor cells, and that TGF-beta secreted and activated by glioblastoma cells suppresses the propagation of immune reaction by inhibiting TNFs secretion by activated lymphocytes adjacent to tumor cells.

Glioblastoma↗

PubMed1994

Roles of prostaglandins and intracellular free calcium mobilisation in epidermal growth factor-induced proliferation of human amnion cells.

OBJECTIVE: To investigate the mechanisms which regulate the growth of human amnion cells. DESIGN: A prospective descriptive study. SUBJECTS: Women undergoing caesarean section at term before the onset of labour. INTERVENTIONS: Amnion cells were cultured in monolayer. MAIN OUTCOME MEASURES: Cell cycle analysis, intracellular calcium levels, prostaglandin (PG) production rates. RESULTS: Epidermal growth factor (EGF) stimulated intracellular Ca2+ mobilisation and PGE2 production in cultured amnion cells. The addition of a Ca2+ channel blocker (cobalt) or a Ca2+ chelator (EGTA) into the culture medium inhibited intracellular Ca2+ mobilisation and PGE2 production induced by EGF. The analysis of cell cycles showed that EGF induced the initiation of DNA synthesis and that the addition of cobalt or EGTA into the culture medium inhibited EGF-induced DNA synthesis. The addition of a cyclo-oxygenase inhibitor (indomethacin) inhibited PGE2 production and DNA synthesis induced by EGF without the effect on intracellular Ca2+ mobilisation. Moreover, the inhibitory effect of indomethacin on EGF-induced DNA synthesis was attenuated by the addition of exogenous PGE2 or PGF2 alpha. CONCLUSIONS: These data suggest that EGF induces an increase in intracellular Ca2+ levels and the rate of prostaglandin production which leads to proliferation of human amnion cells.

Amnion↗

PubMed1994

[Development of the research in the field of histamine release].

Histamine release from mast cells is intimately related with degranulation. When basic histamine releasers such as compound 48/80 were applied extracellularly to isolated rat mast cells by means of microelectrophoresis, localized degranulation was evoked near the tip of micropipet in a few seconds. In response to the second electrophoretic application at the opposite side of the membrane of the same mast cells, similar local degranulation was induced. This fact clearly indicates that local degranulation does not damage mast cells to the extent of blocking following degranulation. As intracellular electrophoretic application of compound 48/80 caused a swelling of mast cell, although no degranulation was elicited. When antigen-antibody reaction was induced in a single rat mesentery mast cell by means of microelectrophoresis, the application of antigen was made extracellularly or intracellularly. At the site of extracellular application, localized degranulation and histamine release were evoked. Histamine release was evidenced by the disappearance of histamine fluorescence in the degranulated area. Neither degranulation nor histamine release was induced by intracellular application of antigen. In freeze-fracture electronmicroscopy of the resting rat mast cells, intra-membrane particles (IMPs) were randomly distributed on the plasma membrane. When sensitized cells were exposed to antigen, IMPs were markedly dispersed so as to surround bulging regions of the membrane elicited by swollen granules. As the particles gathered at the periphery of the bulges, actually no particle was seen on the protuberant region. When rat mast cells loaded with quin 2 were exposed compound 48/80 in a Ca-free medium, a marked increase of quin 2 fluorescence was noticed, indicating that Ca2+ was released from intracellular Ca store. The binding of 45Ca was at its peak in the fractions where the highest activity of glucose-6-phosphatase, a marker enzyme for the endoplasmic reticulum, when organelles of mast cells were fractionated. This may indicate that intracellular Ca store is endoplasmic reticulum. It has been shown that microfilaments, and microtubules play some important roles in histamine release from rat mast cells. When permeabilized mast cells were stimulated with Ca2+, a translocation of protein kinase C from cytosol to membrane fraction was observed. This leads to phosphorylation of vimentin, one of intermediate filaments. In membrane skeletons of rat mast cells, alpha- and beta-fodrin, ankyrin and actin were found by means of western blotting analysis. It was supposed that membrane skeleton may be useful as a barrier between the plasma membrane and the granule membrane.

Actin Cytoskeleton↗

PubMed1994

Improved bioassay for the detection of transforming growth factor-beta 1 and beta 2 in malignant gliomas.

Growth inhibition assays using radioisotope or dye are used to detect transforming growth factor-beta (TGF-beta). Here, we describe a modified bioassay using crystal violet for the quantitative detection of TGF-beta 1 and TGF-beta 2. The procedure is based on staining Mv1Lu mink lung epithelial cells with crystal violet, followed by measurement of the absorbance at 570 nm in individual wells of a 96-well microtiter plate. The number of Mv1Lu cells correlated with the eluted dye intensity. The sensitivity of the bioassay to recombinant TGF-beta 1 and TGF-beta 2 increased approximately twofold by using only 500 Mv1Lu cells in microtiter wells. The bioassay was used to measure TGF-beta activity in the culture supernatant from glioblastoma cells. Culture supernatants were untreated or acid-activated to quantify the active or total TGF-beta, and neutralized with anti-TGF-beta 1 and/or anti-TGF-beta 2 antibody to measure the activity. Both TGF-beta 1 and TGF-beta 2 were detected in the untreated and acid-activated supernatants, and the amounts were calculated by extrapolating from the known recombinant TGF-beta 1 or TGF-beta 2 dilution curve. Our results show that the modified bioassay using crystal violet can measure the levels of TGF-beta 1 and TGF-beta 2 in culture supernatants from malignant glioma cells.

Biological Assay↗

PubMed1994

An autoimmune MRL/Mp-Ipr/Ipr mouse-derived monoclonal IgG antibody stimulates cytokine production in bone-marrow-derived cell line by cross-linking of a cell surface antigen and Fc receptor.

An IgG1 mAb 1G10 derived from an autoimmune MRL/Mp-Ipr/Ipr (MRL/Ipr) mouse has previously been shown to induce IL-3, TNF-alpha and IL-6 production, and autocrine growth in an IL-3-dependent myeloid cell line, FDC-P2/185-4. In the present study, we have attempted to further define the molecular mechanism responsible for the 1G10-induced activation of FDC-P2/185-4 cells. We have shown that 1G10 lacked anti-IgG1 rheumatoid factor activity, failing to generate self-associated immune complexes. Since 1G10 stimulated cells in an Fc gamma R-dependent manner, it seems likely that cross-linking of a cell surface antigen and Fc gamma R by 1G10 antibody is responsible for the stimulation of FDC-P2/185-4 cells. Among several mAb specific to surface antigens expressed on FDC-P2/185-4 cells (MHC class I, LFA-1, and Fc gamma R), only a mAb specific to the alpha chain of LFA-1 alpha was able to induce the IL-3 and Fc gamma R-dependent proliferation of FDC-P2/185-4 cells, similar to that induced by 1G10. Immunoprecipitation analysis revealed that 1G10 recognized a polypeptide with a molecular mass of 140 kilodaltons (p140), which differed from Fc gamma R and from LFA-1 alpha chain. These results suggest that cross-linking of not general but particular cell surface antigens and Fc gamma R stimulates FDC-P2/185-4 cells to produce cytokines resulting in their proliferation.

Animals↗

PubMed1994

Reinforcement effect of histamine on the differentiation of murine myeloblasts and promyelocytes: externalization of granulocyte colony-stimulating factor receptors induced by histamine.

Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF) stimulated the differentiation of murine myeloblasts and promyelocytes to mature neutrophils. In connection with this, myeloperoxidase activity of these progenitor cells was decreased by either histamine or rG-CSF treatment. After pretreatment with histamine at 1 microM, both differentiation and the decrease in myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the number of rG-CSF binding sites on the surface of neutrophil progenitor cells increased after histamine treatment. The histamine-induced increase in rG-CSF binding appeared to be definitely through H2 receptors. Furthermore, the increase in rG-CSF binding sites due to histamine treatment seemed to take place in association with the externalization of G-CSF receptors, because 1) the binding increase was observed in the presence of cycloheximide, 2) no concomitant increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D effectively prevented the increase in rG-CSF binding due to histamine. In neutrophil progenitors, cAMP contents increased very rapidly and significantly after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG-CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However, when progenitor cells were pretreated with protein kinase A inhibitors, the histamine-induced increase in rG-CSF binding was remarkably decreased. This result seems to indicate that the stimulatory effects of histamine on rG-CSF binding to progenitor cells are intimately related to the cAMP-protein kinase A system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil progenitors was markedly reduced by either histamine or rG-CSF treatment. It was concluded that rG-CSF-induced differentiation of murine neutrophil progenitors was augmented by histamine pretreatment mainly due to an increase in rG-CSF receptors on these cells and this increase might be related to the externalization of rG-CSF receptors.

Animals↗

PubMed1994

Effects of antiallergic agents including levocabastine on experimental rhinitis in rats.

Topical application of levocabastine hydrochloride (-)-[3S-[1(cis)-3 alpha,4 beta]]-1-[4-cyano-4-(4-fluorophenyl) cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylic acid monohydrochloride, inhibited the increase in dye leakage into the nasal cavity induced not only by antigen in actively sensitized rats but also by histamine in non-sensitized rats. The potency of levocabastine was stronger than that of ketotifen in inhibiting the increase of dye leakage in both cases. In addition, levocabastine as well as ketotifen exerted a more potent inhibition of the dye leakage induced by histamine than that induced by antigen. Levocabastine also exerted a significant inhibition on the dye leakage induced by substance P; again the effect of levocabastine was more potent than that of ketotifen. On the other hand, levocabastine elicited no remarkable influence on the dye leakage induced by either acetylcholine or platelet activating factor. However, ipratropium and (RS)-2-methoxy-3-(octadecylcarbamoyloxy)propyl 2-(3-thiazolio)ethyl phosphate were effective when the corresponding agonists were perfused, respectively.

Acetylcholine↗

PubMed1994

Molecular mechanism of histamine release: the role of intermediate filaments and membrane skeletons.

It has been recognized that cytoskeletons play some important roles in the histamine release from mast cells. We previously reported the role of microfilaments and microtubules in the histamine release from mast cells, and in the present study, the roles of intermediate filaments and membrane skeletons were investigated. When permeabilized mast cells were stimulated with Ca2+, a translocation of protein kinase C from cytosol to the membrane fraction was observed. This lead to the phosphorylation of vimentin, one of the component proteins of the intermediate filaments. Phosphorylation of vimentin induced disruption of intermediate filaments and resulted in an increase in the mobility of granules. This may be favorable for the initiation of degranulation. In the membrane skeletons of rat mast cells, alpha- and beta-fodrin, ankyrin and actin were found. Changes in the distribution of the fodrin network were elicited by antigen-antibody reaction. It is suggested that membrane skeletons may act as a barrier between the plasma membrane and the granule membrane and that the changes in the distribution of membrane skeletons may facilitate the initiation of the fusion of the plasma membrane and granular membrane.

Animals↗

PubMed1994

Inhibitory effect of epinastine on bronchoconstriction induced by histamine, platelet activating factor and serotonin in guinea pigs and rats.

Effects of epinastine ((+/-)-3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride, WAL 801 CL, CAS 80012-43-7) and reference drugs on bronchoconstriction induced by histamine, platelet activating factor (PAF) and serotonin were studied in guinea pigs and rats. Oral administration of epinastine resulted in a potent inhibition on bronchoconstriction induced by all three bronchoconstrictor agents, and especially, an inhibitory effect on histamine-induced response was remarkable. The effect of epinastine was stronger than that of ketotifen in inhibiting the responses induced by both PAF and serotonin. However, the extent of inhibition in the latter was less remarkable than that seen after histamine. Azelastine was 1.36-4.57 times less potent than epinastine in inhibiting the bronchoconstriction induced by either bronchospasmogen. Although promethazine displayed inhibitory effects on the responses induced by histamine, PAF and serotonin, the inhibiting potency was distinctly inferior to that of epinastine.

Airway Resistance↗

PubMed1993

High magnesium concentration inhibits ligand-stimulated calcium influx and hormone secretion in rat pituitary lactotropes with involvement of intracellular free magnesium.

The effects of extracellular magnesium concentration ([Mg2+]ex) on thyrotropin-releasing hormone (TRH)-stimulated intracellular free calcium mobilization and prolactin secretion were investigated concomitantly with measurement of the intracellular free magnesium concentration ([Mg2+]i). TRH-stimulated intracellular free calcium mobilization was significantly inhibited when the medium was replaced by high Mg2+ medium ([Mg2+]ex = 10 mM) in normal Ca2+ medium. The inhibitory effects of high Mg2+ became apparent concomitantly with an increase in [Mg2+]i from 0.7 to 1.3 mM. High Mg2+ significantly inhibited TRH-induced PRL secretion in a dose-dependent manner in normal Ca2+ medium. TRH-stimulated inositol triphosphate (IP3) production was rather augmented by the replacement with high Mg2+ medium. In summary, high Mg2+ inhibits Ca2+ influx stimulated by TRH in the rat pituitary lactotropes, possibly with the involvement of [Mg2+]i increase. These results have general importance in relation to high Mg(2+)-induced suppression of the biological functions of cells.

Animals↗

PubMed1993

Dynamics of exocytosis, endocytosis and recycling in single pituitary gonadotropes.

The dynamic changes in exocytosis, endocytosis and recycling in single gonadotropes induced by gonadotropin-releasing hormone (GnRH) were visualized and estimated with an impermeable fluorescent membrane probe, 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatrien (TMA-DPH), using a digital imaging and confocal laser scanning microscope. 10(-7) M GnRH induced exocytosis and endocytosis within 10 sec and 60 sec, respectively. Recycling of the plasma membrane started at 180-300 sec. Exocytosis and endocytosis in purified gonadotropes changed dose-dependently with 10(-10)-10(-7) M GnRH. These results show that GnRH-induced exocytosis, endocytosis and recycling in gonadotropes maintain dynamic equivalence. The procedure we established will be very useful in studies of the function of secretory cells.

Animals↗

PubMed1993

The role of c-Jun protein in thrombin-stimulated expression of preproendothelin-1 mRNA in porcine aortic endothelial cells.

Treatment of porcine aortic endothelial cells with thrombin induced a time- and dose-dependent expression of preproendothelin-1 (PPET-1) mRNA. The thrombin-induced expression of PPET-1 mRNA was markedly inhibited by calphostin C, a specific inhibitor of protein kinase C, and phorbol 12-myristate 13-acetate (TPA) induced the expression of PPET-1 mRNA dose-dependently, but 4 alpha-phorbol 12, 13-didecanoate, an inactive enantiomer of phorbol ester, had no effect on the expression of PPET-1 mRNA. On the other hand, challenge of the endothelial cells with thrombin induced a marked and time-dependent increase in the binding activity of nuclear extract to the TPA-responsive element. Furthermore, thrombin elicits synthesis of c-Jun protein as well as triggering its dephosphorylation. From these results, it is concluded that thrombin-stimulated expression of PPET-1 mRNA in porcine aortic endothelial cells can be induced not only by c-Jun protein synthesis but also by initial dephosphorylation in response to activation of protein kinase C.

Animals↗

PubMed1993

Influence of histamine depletion on learning and memory recollection in rats.

To clarify the role of endogenous histamine in learning and memory, the effect of alpha-fluoromethylhistidine on active avoidance response in rats was studied. alpha-Fluoromethylhistidine (20-100 mg/kg or 10-50 micrograms) significantly (P < 0.05 or P < 0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms) significantly (P < 0.05 or P < 0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When alpha-fluoromethylhistidine (50 micrograms) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats.

Animals↗

PubMed1993

Magnesium sulfate inhibits oxytocin-induced calcium mobilization in human puerperal myometrial cells: possible involvement of intracellular free magnesium concentration.

OBJECTIVE: Our purpose was to elucidate the mechanisms of the tocolytic action of Mg2+ on the human myometrium. STUDY DESIGN: The effects of extracellular Mg2+ on oxytocin-induced increases in the intracellular free Ca2+ concentration in human puerperal myometrial cells were examined by means of indo-1-AM. The changes in the intracellular free Mg2+ concentration under various conditions were also measured with Mg(2+)-fura-2-AM. RESULTS: The increase in intracellular free Ca2+ concentration induced by oxytocin was reduced to 26% of that in the normal solution 20 minutes after replacement of the normal solution with an extracellular Mg2+ solution, 10 mmol/L. When extracellular Ca2+ was removed, the increase in intracellular free Ca2+ concentration was not suppressed even 20 minutes after the replacement. A solution of extracellular Mg2+ concentration, 10 mmol/L, raised the intracellular free Mg2+ concentration gradually, by approximately 150% in 20 minutes, concomitant with the suppression of the response to oxytocin in the intracellular free Ca2+ concentration. CONCLUSION: High intracellular free Mg2+ concentration, caused by high extracellular Mg2+, is essential for suppression of oxytocin-induced Ca2+ influx across the cell membrane; this presumably results in inhibition of uterine contractions.

Calcium↗

PubMed1993

The pathway responsible for EEG synchronization and effect of histamine on this system.

Electrical stimulation (3 Hz, 0.5 volts) to the midbrain reticular formation of conscious rats induced significant increase of EEG power densities (synchronization) recorded at the frontal cortex (FCOR), nucleus ventralis thalami (VE), or nucleus medialis centralis thalami (CM). Significant synchronization was also observed in the FCOR when electrical stimulation was applied to the VE and CM. When ipsilateral and bilateral VEs were electrocoagulated, no EEG synchronization was observed in the FCOR and CM. Intracerebroventricular administration of histamine (Hi) caused a marked suppression of FCOR EEG synchronization in both CM-lesioned and normal rats through H1 receptors. EEG synchronization in FCOR was not induced in ipsilateral or bilateral VE-lesioned rats after RF stimulation. When Hi (1 microgram) was injected into the VE of normal rats, EEG synchronization of FCOR was markedly reduced after RF or VE stimulation. No such changes were induced when Hi was injected into the CM.

Animals↗

PubMed1993

Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an increase in plasma corticosterone concentration. Even in hypophysectomized rats, a significant increase in plasma corticosterone concentration was induced by histamine at doses of 20 and 50 micrograms kg-1. 3. Histamine at doses of 10 and 20 micrograms kg-1 elicited an increase in the amplitude of adrenal nerve activity, and electrical stimulation to the adrenal nerves resulted in an increase in plasma corticosterone concentration. 4. Both H1-agonist (2-methylhistamine) and H2-agonists (4-methylhistamine and impromidine) also induced similar effects to those of histamine. Pretreatment with pyrilamine caused an inhibition of histamine-induced increase in plasma ACTH and corticosterone concentrations, while both cimetidine and ranitidine failed to inhibit this effect. However, both H2-blockers were effective in inhibiting the 4-methylhistamine-induced elevation of plasma ACTH and corticosterone concentrations. 5. Neither (R)-alpha-methylhistamine nor thioperamide had a significant effect, indicating that the H3-receptor is not involved in the histamine-induced increase in plasma ACTH and corticosterone concentrations. 6. From these findings, it was concluded that (1) electrical signals transmitted from the brain to the adrenal gland through the neurones may be involved in the rapid corticosterone release induced by histamine, and (2) not only H1- but also H2-receptors are implicated in histamine-induced hormone secretions in rats, though the contribution of the H2-receptor is less important than that of the H1-receptor.

Adrenal Glands↗