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Biomedical subjects

M Arisawa

Publications and source records attributed to M Arisawa.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Characterization of the calcitonin gene-related peptide receptor in mouse T lymphocytes.

We have identified and characterized specific binding for calcitonin gene-related peptide (CGRP) in mouse T lymphocytes. The binding of 125I-CGRP to mouse lymphocytes was reversible and the rate of dissociation of 125I-CGRP increased with the addition of the guanine triphosphate nucleotide analog, Gpp(NH)p. Saturation experiments, and Scatchard analysis indicated two classes of binding sites for CGRP; the apparent dissociation constants (KD) were 3.5 X 10(-10)M for high affinity binding sites (Bmax, 265 sites/cell) and 4.8 X 10(-8)M for low affinity binding sites (Bmax, 13,000 sites/cell). The KD value for the high affinity binding sites is roughly comparable to the IC50 and ED50 values for inhibition of T lymphocyte proliferation and increase in the cyclic AMP concentration in these cells, respectively. 125I-CGRP bound to mouse T lymphocytes was displaced by unlabeled CGRP with an IC50 value of 3.2 X 10(-10)M; salmon or human calcitonins did not inhibit the specific binding up to 1 X 10(-6)m. Our studies suggest that CGRP may be an important immunoregulatory molecule, and implicate it in the regulation of T cell function.

Animals↗
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Mutagenicity examination of several non-steroidal anti-inflammatory drugs in bacterial systems.

The mutagenicity of 6 marketed non-steroidal anti-inflammatory drugs (aspirin, flufenamic acid, diclofenac sodium, indomethacin, naproxen and chloroquine) as well as 2 new anti-inflammatory drugs (tenoxicam and carprofen) was examined by using in vitro bacterial systems (repair test and reversion test). None of them was mutagenic on Ames' reversion test. However, they differed in their responses to repair tests. Tenoxicam, carprofen, aspirin, flufenamic acid and naproxen were not mutagenic in either rec- or pol-assays, whereas chloroquine only showed positive results in the pol-assay system. Indomethacin and diclofenac sodium exhibited a slightly stronger inhibitory activity against B. subtilis rec- mutant than against its rec+ counterpart in rec-assay, which was much weaker than AF-2. Thus their mutagenicity was questionable. These results confirm the usefulness of DNA-repair assays as a complementary endpoint to gene mutation in assessing the genotoxic potential of environmental compounds.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Effects of the gonadotropin-releasing hormone associated peptides (GAP) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in vivo.

Six peptide sequences residing between basic amino acid residues in GAP were tested for effects on the release of FSH, LH and PRL in vivo in ovariectomized, estrogen-progesterone-primed (OEP) rats. Synthetic GAP peptides (1-13, 1-23, 15-23, 25-36, 38-53 and 41-53) were injected intravenously (IV) into conscious OEP rats and plasma levels of FSH, LH and PRL were measured by RIA. The activity of GAP peptides in the control of PRL was further examined in ether-stressed male rats which were injected IV with GAP peptides just prior to a 1-min etherization. GAP(1-13) significantly stimulated FSH release at doses of 1, 10 and 100 micrograms, whereas it stimulated LH release only at the highest dose of 100 micrograms. GAP(1-23) elevated plasma levels of FSH and LH only at a dose of 100 micrograms. The other 4 peptides had no effect on the release of gonadotropins. Of these 6 peptides, only GAP(1-13) partially lowered the plasma levels of PRL at the high dose of 100 micrograms in OEP rats, but it had no effect on the ether-induced PRL surge at doses of 10 and 100 micrograms. In conclusion, both GAP(1-13) and GAP(1-23) stimulate FSH and LH release in vivo; these 2 peptides are much less potent in stimulating gonadotropin release than is LHRH. GAP(1-13) exerts a preferential FSH-releasing activity, but its PRL-inhibiting activity is minimal.

Animals↗
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Effect of substance P on thyrotropin secretion from the pituitary gland in the rat.

The role of substance P (SP) on thyrotropin (TSH) secretion was investigated in ovariectomized (OVX) female, estrogen-primed OVX, and normal male rats. Third ventricular administration of SP induced a significant increase in plasma TSH levels when compared to control animals in E-primed OVX rats (p less than 0.001). The plasma TSH levels increased in a dose-related manner and reached maximum levels at 10 min after injection. In contrast, intraventricularly injected SP failed to alter plasma TSH levels in both OVX rats and normal male rats. Intravenous administration of SP dramatically stimulated TSH release in E-primed OVX rats (p less than 0.001), whereas SP had no effect on the release of TSH when injected in OVX rats and normal male rats. To investigate any direct action of SP on TSH release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats and normal male rats. SP, in the dose range between 10(-8) M and 10(-6) M, failed to alter the release of TSH into the culture medium in vitro. These findings indicate that SP has a stimulatory role in the control of TSH release by an action on the hypothalamus but only in estrogen-primed rats.

Animals↗
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Activation of CCK-B receptors elevates cytosolic Ca2+ levels in a pituitary cell line.

Cytosolic Ca2+ levels ([Ca2+]i) in GH3 cells, a rat anterior pituitary tumor cell line, were monitored with fura-2 by fluorescence measurements. Cholecystokinin octapeptide (CCK-8) produced a transient elevation of [Ca2+]i. The elevation of [Ca2+]i by CCK-8 was inhibited by L-365,260, but not by devazepide. It was still observed when extracellular Ca2+ was eliminated, indicating that CCK-8 mobilizes Ca2+ from intracellular storage sites after interaction with CCK-B receptors. Cholecystokinin octapeptide increased the turnover of phosphatidylinositol, but it did not affect cyclic AMP levels. A possible involvement of phosphatidylinositol breakdown and calcium mobilization in the transduction system of CCK-B receptors in GH3 cells is suggested.

Animals↗
PubMedDate not supplied

GH3 cells, an anterior pituitary cell line, express CCK-B receptors.

We found that GH3 cells, a rat anterior pituitary tumor cell line, expressed a single class of high-affinity binding sites for radiolabeled cholecystokinin octapeptide (CCK-8) with a Kd of 48 pM. The binding sites had high affinity for CCK-8, CCK-4, gastrin I, and L-365,260 (CCK-B antagonist), and had low affinity for devazepide (CCK-A antagonist), indicating that the binding sites are CCK-B receptors. GTP and its stable analogues inhibited radiolabeled CCK-8 binding to GH3 cell membranes, suggesting a coupling of CCK-B receptors to a G-protein.

Animals↗
PubMedDate not supplied

Plant anticancer agents. XXIII. 6 alpha-senecioyloxychaparrin, a new antileukemic quassinoid from Simaba multiflora.

Fractionation of an aqueous ethanol extract of the wood of Simaba multiflora afforded a new antineoplastic quassinoid, 6 alpha-senecioyloxychaparrin (5), and two known quassinoids 6 alpha-senecioyloxychaparrinone (1) and chaparrinone (2). The structure of 5, which displayed activity against the KB and P-388 test systems, was established through the interpretation of spectral data.

Acetylation↗
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Plant anticancer agents. XXIV. Alkaloid constituents of Simaba multiflora.

Two new cytotoxic canthin-6-ones, 10-methoxycanthin-6-one (1) and 10-hydroxycanthin-6-one (2) were isolated from the wood of Simaba multiflora (Simaroubaceae). Three canthin-2,6-dione (3), 3-methoxycanthin-2,6-dione (4) and canthin-2,6-dione (5), as well as scopoletin (7) and the novel coumarino-lignan cleomiscosin A (6) were also obtained.

Acetylation↗
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Potential anticancer agents XXXI. N-demethylation of fagaronine.

Fusion of fagaronine (1) afforded N-demethyl fagaronine (2) and two minor desmethyl products. Through examination of spectral properties and derivatization, the structures were deduced to be 3, a tetramethoxy derivative, and 5, a derivative bearing a hydroxy (rather than a methoxy) group at position-8. Acetylation of 2 afforded a monoacetate derivative (4), and similarly, a diacetate (6) was produced from 5. Compounds 2-6 were substantially less cytotoxic than 1, as judged by KB or P-388 cell culture assays, supporting the functional importance of the quaternary nitrogen atom. The results obtained to date for fagaronine in tumor panel-testing are also presented, and the marginal cytotoxic activity demonstrated by compounds 5 and 6 against cultured P-388 cells is discussed in terms of mechanisms of action of the parent compound.

Alkaloids↗
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Studies on cytotoxic constituents in pericarps of Mallotus japonicus, Part I.

Two new phloroglucinol derivatives, named mallotophenone and mallotochromene, were isolated from the pericarps of Mallotus japonicus together with two known compounds, 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)-phloracetophenone and 2,6-dihydroxy-3-methyl-4-methoxyacetophenone. The new derivatives were confirmed to be 5-methylene-bis-2,6-dihydroxy-3-methyl-4-methoxyacetophenone and 8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)2,2-dimethylchromene by their respective chemical and spectral data. Several of the phloroglucinol derivatives isolated from this tree were cytotoxic against the KB system and L-5178Y in cell culture.

Acetylation↗
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Studies on cytotoxic constituents in pericarps of Mallotus japonicus, Part II.

Two new phloroglucinol derivatives, mallotolerin (8) and mallotochromanol (9), were isolated from the cytotoxic fraction of the pericarps of Mallotus japonicus. The new derivatives were identified as 3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-5-me thy l-6- methoxybenxyl)-phlorbutyrophenone (8) and 8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenxyl)2,2-dimethyl-3-hydroxychroman (9) by their respective chemical and spectral data. These compounds were found to be cytotoxic against KB and L-5178Y cell lines in culture and to be moderately effective in inhibiting the growth of Ehrlich carcinoma in mice. Cytotoxic activities of the isolated phloroglucinol derivatives (1-9) from the pericarps are also discussed.

Acetylation↗
PubMedDate not supplied

Three new lanostanoids from Ganoderma lucidum.

Three new lanostanoids--ganodermenonol (1), ganodermadiol (2), and ganodermatriol (3) [isolated as its triacetate derivative (3a)]--were isolated from the MeOH extract of Ganoderma lucidum, together with ergosterol and its peroxide. The new compounds were identified as 26-hydroxy-5 alpha-lanosta-7,9(11),24-trien-3-one (1), 5 alpha-lanosta-7,9(11),24-triene-3 beta, 26-diol (2), and 5 alpha-lanosta-7,9(11),24-triene-3 beta, 26,27-triol (3) by their respective spectral data.

Acetylation↗