AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP...AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.展开更多
Objective To explore the role of endothelin (ET) in the pathogenesis of exercise induced asthma (EIA), we investigated the effects of ET B receptor antagonists, ET 1 11 21 fragment and N cis 2,6 dimethylp...Objective To explore the role of endothelin (ET) in the pathogenesis of exercise induced asthma (EIA), we investigated the effects of ET B receptor antagonists, ET 1 11 21 fragment and N cis 2,6 dimethylpi^peridinocardonyl L γ methylleucyl D 1 methoxycarbonyl tryptophanyl D norleucine (BQ788) on broncho^constriction elicited by isocapnic hyperpnea in guinea pigs Methods Eighteen pathogen free Hartley guinea pigs were randomly divided into three groups A: normal saline (NS) inhalation control group (n=6), B: BQ788 group (n=6), and C: ET 1 11 21 fragment group (n=6) Guinea pigs were anesthetized with pentobarbital sodium After measuring the basal value of lung resistance (R L) and dynamic compliance of the respiratory system (Cdyn), NS (0 96?ml), BQ788 (9?nmol) and ET 1 11 21 fragment (9?nmol) were inhaled A rodent respirator with a dry 5%CO 2-95%O 2 mixture at room temperature provided mechanical ventilation (V T 8?ml/animal, 100 breaths/min) for 5?min R L and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in R L and decrease in Cdyn R L and Cdyn of the guinea pigs from BQ788 group and ET 1 11 21 fragment group did not change significantly Conclusion It was demonstrated that selective ET B receptor antagonists, ET 1 11 21 fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors It was suggested that ET receptor antagonists, especially ET B receptor antagonist, might be beneficial in preventing EIA展开更多
Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of th...Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of this study was to investigate whether the over expressed tropoelastin in epidermis has some role in melanogenesis of melanocytes. Methods A375 human melanoma cells were treated with different concentrations of kappa elastin for 24 hours. A375 human melanoma cells were randomly assigned to control, kappa elastin, and lactose pre-incubated groups. The cell viabilities were detected by the methyl thiazoleterazolium assay. Melanin content and tyrosinase activity in A375 melanoma cells were measured. The expressions of endothelin B receptor （ETBR） mRNA and c-kit mRNA in A375 melanoma cells were measured by quantative reverse transcription polymerase chain reaction. Results Fifty pg/ml of kappa elastin significantly increased the melanin content by 56.64% compared with the control （P 〈0.05）. Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the control at 24 hours （P 〈0.05）. Kappa elastin increased the expressions of ETBR and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls, respectively. When pre-incubating cells with a lactose solution （10 mmol/L）, the inhibition on melanin production was 34.96% compared with the kappa elastin group （P 〈0.05）, tyrosinase activity was inhibited by 29.93% compared with kappa elastin group （P 〈0.05）, and the expressions of ETBR mRNA and c-kit mRNA were decreased by 1.56-fold and 0.82-fold compared with kappa elastin group, respectively. Conclusion Kappa elastin increased the melanogenesis in A375 melanoma cells via the stimulation of tyrosinase activity and the expression of ETBR and c-kit. The over expressed tropoelastin produced by keratinocytes might play a role in melanogenesis of epidermal melanocytes.展开更多
基金Supported by Grant from National Key New Drug Creation Project of China, No. 2009ZX09102
文摘AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.
文摘Objective To explore the role of endothelin (ET) in the pathogenesis of exercise induced asthma (EIA), we investigated the effects of ET B receptor antagonists, ET 1 11 21 fragment and N cis 2,6 dimethylpi^peridinocardonyl L γ methylleucyl D 1 methoxycarbonyl tryptophanyl D norleucine (BQ788) on broncho^constriction elicited by isocapnic hyperpnea in guinea pigs Methods Eighteen pathogen free Hartley guinea pigs were randomly divided into three groups A: normal saline (NS) inhalation control group (n=6), B: BQ788 group (n=6), and C: ET 1 11 21 fragment group (n=6) Guinea pigs were anesthetized with pentobarbital sodium After measuring the basal value of lung resistance (R L) and dynamic compliance of the respiratory system (Cdyn), NS (0 96?ml), BQ788 (9?nmol) and ET 1 11 21 fragment (9?nmol) were inhaled A rodent respirator with a dry 5%CO 2-95%O 2 mixture at room temperature provided mechanical ventilation (V T 8?ml/animal, 100 breaths/min) for 5?min R L and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in R L and decrease in Cdyn R L and Cdyn of the guinea pigs from BQ788 group and ET 1 11 21 fragment group did not change significantly Conclusion It was demonstrated that selective ET B receptor antagonists, ET 1 11 21 fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors It was suggested that ET receptor antagonists, especially ET B receptor antagonist, might be beneficial in preventing EIA
基金This study was supported by a grant from the National Natural Science Foundation of China
文摘Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of this study was to investigate whether the over expressed tropoelastin in epidermis has some role in melanogenesis of melanocytes. Methods A375 human melanoma cells were treated with different concentrations of kappa elastin for 24 hours. A375 human melanoma cells were randomly assigned to control, kappa elastin, and lactose pre-incubated groups. The cell viabilities were detected by the methyl thiazoleterazolium assay. Melanin content and tyrosinase activity in A375 melanoma cells were measured. The expressions of endothelin B receptor （ETBR） mRNA and c-kit mRNA in A375 melanoma cells were measured by quantative reverse transcription polymerase chain reaction. Results Fifty pg/ml of kappa elastin significantly increased the melanin content by 56.64% compared with the control （P 〈0.05）. Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the control at 24 hours （P 〈0.05）. Kappa elastin increased the expressions of ETBR and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls, respectively. When pre-incubating cells with a lactose solution （10 mmol/L）, the inhibition on melanin production was 34.96% compared with the kappa elastin group （P 〈0.05）, tyrosinase activity was inhibited by 29.93% compared with kappa elastin group （P 〈0.05）, and the expressions of ETBR mRNA and c-kit mRNA were decreased by 1.56-fold and 0.82-fold compared with kappa elastin group, respectively. Conclusion Kappa elastin increased the melanogenesis in A375 melanoma cells via the stimulation of tyrosinase activity and the expression of ETBR and c-kit. The over expressed tropoelastin produced by keratinocytes might play a role in melanogenesis of epidermal melanocytes.
