To investigate the mechanisms underlying itching in atopic dermatitis, we examined whether thromboxane (TX) A2, an arachidonic acid metabolite, is involved in spontaneous scratching, an itch-related response, in NC mice with atopic dermatitis-like skin lesions. The TXA2 receptor (TP) antagonist ONO-3708 inhibited the spontaneous scratching. The mRNA expression of TX synthase (TXSyn) distributed mainly in epidermis and the concentration of TXB2, a metabolite of TXA2, were increased in lesional skin. Scratching caused by the PAR2 agonist SLIGRL-NH2 was suppressed by ONO-3708. SLIGRL-NH2-induced scratching decreased approximately 75% in TP-deficient mice, compared to wild-type mice. In primary cultures of mouse keratinocytes, SLIGRL-NH2 induced the production of TXA2, as evidenced by the increased TXB2, which was inhibited by the TXSyn inhibitor sodium ozagrel and a PAR2-neutralizing antibody. Taken together, these results suggest that epidermal TXA2, which may be produced via PAR2 activation, is involved in itching in atopic dermatitis.

01 Jan 2016·The American Journal of Chinese Medicine

Antagonistic Effects ofGingko bilobaandSophora japonicaon Cerebral Vasoconstriction in Response to Histamine, 5-Hydroxytryptamine, U46619 and Bradykinin

Article

Author: Islam, Md. Zahorul ; Pothinuch, Pitchaya ; Nguyen, Thanh Van ; Dao, Cuong Van ; Miyamoto, Atsushi ; Nguyen, Hai Thanh ; Nguyen, Ha Thi Thanh ; Nguyen, Tuong Manh ; Shiraishi, Mitsuya ; Obi, Takeshi

The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca[Formula: see text], histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9[Formula: see text],11[Formula: see text]-methanoepoxy prostaglandin (PG) F[Formula: see text](U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm. Isolated porcine basilar arteries (PBA) and endothelial cells from them were used as the study materials. Neither SJ nor GB had any effect on the contractions induced by KCl and extracellular Ca[Formula: see text]. SJ significantly inhibited the contraction induced by histamine, 5-HT, U46619 and BK, whereas GB inhibited histamine-induced contraction, but had no effects on the contractions induced by 5-HT, U46619 and BK. In the presence of diphenhydramine (a H1receptor antagonist), ketanserin (a 5-HT2receptor antagonist) and ONO-3708 (a thromboxane (TX) A2/PG receptor antagonist), the inhibitory effects of these extracts on the contractions induced by histamine, 5-HT and U46619 were abolished. SJ significantly inhibited the contractions induced by BK and PGF[Formula: see text], but in the presence of ONO-3708 (10[Formula: see text] M) had no effect on them. BK enhanced the production of PGF[Formula: see text] from cultured PBA endothelium cells, and SJ significantly attenuated this enhancement. These results suggest that SJ and GB have a H1-antagonistic effect, and that SJ also attenuates cerebral vasoconstriction mediated via 5-HT2and TXA2/PG receptors. These findings appear to explain why SJ has been used traditionally as a therapeutic medication for cerebral vasospasm after cerebral hemorrhage.

01 Mar 2009·Critical Care MedicineQ1 · MEDICINE

Differential responses of porcine anterior spinal and middle cerebral arteries to carbon dioxide and pH

Q1 · MEDICINE

Article

Author: Yunokawa, Seki ; Gamou, Sanae ; Morita, Shigeho ; Shimoji, Koki ; Fukuda, Satoru ; Sakamoto, Hidetoshi ; Kokubun, Seiichiro ; Ogura, Mai

OBJECTIVEDysfunction of the anterior spinal arteries (ASAs) may induce paresis or paraplegia after thoracoabdominal aortic aneurysm or spine surgery. However, there have been no reports of the effects of CO2 and pH on ASAs. Information on these effects on ASAs might contribute to the perioperative management or critical care of spinal cord function. Thus, we investigated the effects of CO2 and pH on the vasomotor tone of ASAs and the third branch of the middle cerebral artery (bMCA).DESIGNProspective study of the effects of CO2 and pH on vasomotor response of porcine ASA and bMCA in vitro.SETTINGUniversity laboratories.SUBJECTSPorcine heads and spinal cords obtained from a slaughterhouse.INTERVENTIONASAs and bMCAs were isolated, and changes in the intraluminal region of these pressurized arteries ( approximately 80 mm Hg) were observed for 30 minutes after perfusion with a solution saturated with various concentrations of CO2 and pH.MEASUREMENTS AND MAIN RESULTSRespiratory acidosis (pH/Pco2 approximately 7.10-7.15/ approximately 60-80 mm Hg) constricted the ASAs, followed by a partial but gradual decrease in tone, whereas the bMCAs were exclusively dilated. The respiratory alkalosis (pH/Pco2 approximately 7.60/ approximately 20 mm Hg) did not influence ASA tone. Vasoconstriction of the ASAs induced by respiratory acidosis was abolished by removal of the endothelium, but not by N-nitro-L-arginine (1 microM). Respiratory acidosis dilated the ASAs in all preparations treated with ONO-3708 (1 microM), a specific thromboxane A2 receptor antagonist, and OKY-046 (1 microM), a specific thromboxane synthase inhibitor. Metabolic acidosis (pH/Pco2 approximately 7.10/ approximately 40 mm Hg) caused dilation of both bMCAs and ASAs, which was abolished by glibenclamide (1 microM).CONCLUSIONSCO2-induced endothelium-dependent constriction in porcine ASAs through releasing thromboxane A2-like substance(s). Thus, hypercarbia might not be favorable for the perioperative or critical care management of spinal cord function during thoracoabdominal aortic aneurysm and spine surgery.

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Discovery	JP	Ono Pharmaceutical Co., Ltd.	-

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