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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 343 records · Page 19Linked to original sources

Histamine release induced by neurotensin from rat peritoneal mast cells.

Neurotensin induced the release of histamine from both purified and non-purified rat peritoneal mast cells by a non-cytotoxic mechanism. It was effective at a concentration as low as 10(-8) M. The dose-response curve for the neurotensin effect was triphasic: and initial gentle rise, a plateau (2.5 X 10(-7) -2.5 X 10(-6) M) and a second rise. Disodium cromoglycate markedly, but benzalkonium chloride only slightly, inhibited the neurotensin-induced release. The effect of neurotensin was markedly different from that of substance P, bradykinin and compound 48/80 with respect to both the dose-response curve and the sensitivity to benzalkonium chloride. These inducers of histamine release showed somewhat different effects with changes in pH and temperature. Their actions did not require extracellular Ca2+. The results indicate that neurotensin is a potent histamine releaser acting directly on mast cells. Its mode of action may be different from those of the other substances tested.

Animals↗

Histamine release from rat mast cells sensitized with mouse antiserum.

The characteristics of the antigen-induced and non-antigen-induced histamine release from rat peritoneal mast cells sensitized in vitro with mouse anti-ovalbumin serum were investigated. The effects of some antiallergic drugs on these release reactions were also studied. Besides antigen-specific IgE antibody, heat-labile factor(s) responsible for the non-antigen-induced histamine release were found in mouse antiserum. Such factors were also present in normal mouse serum. In the absence of antigen, the combination of phosphatidyl serine and Ca++ induced some extent of histamine release from mast cells treated with these factors. From the present results it is suggested that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and disodium cromoglycate selectively inhibit the passage of calcium through open calcium channels.

Animals↗

Effect of histamine on cyclic AMP levels in the submandibular gland.

Histamine and 4-methylhistamine increased on cyclic AMP level in chopped guinea-pig submandibular glands. 4-Methylhistamine was more active than histamine. 2-(2-Pyridyl)ethylamine was less active than histamine or almost inactive. Metiamide markedly antagonized the histamine-induced cyclic AMP increase but mepyramine had no inhibitory effect on this increase. These results suggest that there are H2-receptors which mediate the cyclic AMP response to histamine in the guinea-pig submandibular gland.

1-Methyl-3-isobutylxanthine↗

Cyclic AMP increase by histamine and its analogues in guinea-pig submandibular gland.

The effect of histamine and its analogues on the cyclic AMP level in chopped guinea-pig submandibular glands was investigated. These agonists increased the cyclic AMP level dose-dependently. The ED50 values for histamine and 4-methylhistamine were approximately 1.3 x 10(-5) M and 2.2 x 10(-5) M, respectively. The efficacy of 4-methylhistamine was higher than that of histamine. 2-(2-Pyridyl)-ethylamine was far less effective compared with histamine or 4-methylhistamine. Metiamide markedly antagonized the cyclic AMP response to histamine and 4-methylhistamine, but mepyramine was ineffective. A combination of aminoguanidine and quinacrine had no influence on the effect of histamine on the cyclic AMP level. These results indicate the H2-type histamine receptors which mediate the cyclic AMP increase are present in the guinea-pig submandibular gland.

Animals↗

Inhibition of adjuvant arthritis by salbutamol and aminophylline.

Salbutamol (3 mg/kg) and aminophylline (75 mg/kg) were administered s.c. to rats separately or in combination after intradermal injection of adjuvant into the left hind paw. The paw volume was measured plethysmographically; tissue cyclic AMP content was determined by a protein binding assay following whole body microwave irradiation. The combination of salbutamol and aminophylline given daily significantly inhibited the swelling response in both the adjuvant-injected and the non-injected paws. This drug combination significantly increased the cyclic AMP levels in inflamed tissue of the adjuvant-injected hind paw and in lymphoid tissue such as the spleen and thymus. The combined treatment seems to have immunosuppressive as well as anti-inflammatory effects on adjuvant-induced arthritis.

Albuterol↗

Decrease in peritoneal mast cell count in rats with adjuvant arthritis. I. Time course and interstrain difference.

Adjuvant was injected into the left hind paw of Sprague-Dawley (SD) and Wistar rats. In SD rats a marked decrease in the mast-cell count and histamine content of the peritoneal fluid and a significant increase in the histamine content as well as the mast-cell count in the mesentery appeared between 1 and 2 weeks after adjuvant injection. This period approximately coincided with that of the development of secondary inflammatory lesions such as polyarthritis. The adjuvant-induced changes in the peritoneal fluid were more marked in SD than in Wistar rats, corresponding to more intense adjuvant arthritis in the SD strain. In Wistar rats a tendency towards an increase in the histamine content of the mesentery was observed from 2 weeks after adjuvant injection. Adjuvant injection did not have any significant effect on the histamine content of the caecum or the skin of either strain. These results show that adjuvant causes a redistribution of mast cells between the peritoneal fluid and the tissues surrounding the peritoneal cavity probably as a result of delayed hypersensitivity.

Animals↗

Effects of BCG, levamisole and PS-K on the rejection of male skin grafts by female mice.

Rejection of male skin grafts by BALB/c female mice was accelerated by one s.c. injection of BCG (5 X 10(5) microorganisms/mouse) into recipients on the day of transplantation. Levamisole 20 mg/kg injected similarly was without any effect. Protein-bound polysaccharide Kureha (PS-K) injected 250 mg/kg s.c. or i.p. once every other day from the day of transplantation stimulated graft rejection. The s.c. route was more effective than the i.p. route. These results show that, in sex-linked graft rejection in mice, PS-K has an immunostimulant action similar to that of BCG. This property may be important to the antineoplastic activity of PS-K.

Animals↗

Inhibition of adjuvant arthritis by histamine.

Histamine was injected subcutaneously to rats at doses of 2--10 mg/kg, twice daily for various periods after an intradermal adjuvant injection into one hind paw. The administration of histamine prevented the appearance of the secondary lesion in the noninjected paw, but did not affect the primary swelling of the injected paw or the established secondary lesion. The histamine effect was dose-dependent with the most effective time of administration being from the 5th to the 10th day after adjuvant injection. Arthritic lesions found in control animals in histological and roentgenographic examinations were also inhibited in histamine-treated animals. Sinomenine, a histamine releaser, likewise showed a suppressive effect on the secondary lesion. Burimamide, a histamine H2-receptor antagonist, blocked these histamine effects, while mepyramine, a H1-receptor antagonist, did not have such a blocking effect. The findings suggest that histamine may inhibit the development of adjuvant arthritis by an immunosuppressive mechanism mediated through activation of H2-receptors on lymphoid cells.

Adjuvants, Immunologic↗

Inhibition of granulation tissue growth by histamine.

Granulomas were induced in rats by subcutaneous implantation of formalin-soaked filter-paper disks. Daily subcutaneous injection of histamine at doses of two times 0.05 mg/kg and above inhibited the growth of granulation tissue as measured by a marked decrease in the dry-defatted granuloma weight and of the hydroxyproline and hexosamine content. Histological observations of granulation tissue indicated that histamine inhibited the proliferation of fibroblasts and the formation of capillaries. Inhibitory effects were also observed with the histamine releaser, sinomenine, and the histaminase inhibitor, aminoguanidine. These histamine effects seem not to be mediated by glucocorticoid release, since an effective dose level of histamine produced no change in growth or thymus weight. Prednisolone was less potent than histamine in inhibiting Prednisolone was ineffective at the dose tested. Subcutaneous injection of the H2-receptor antagonist, burimamide, blocked these histamine effects and also of sinomeinine and aminoguanidine. The H1-receptor antagonist, mepyramine, did not block these histamine effects. Burimamide alone enhanced the growth of granuloma. These results indicate that granulation-tissue growth in inflammation is affected by the inhibitory effect of endogenous histamine acting through H2-receptors.

Amine Oxidase (Copper-Containing)↗