AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially wi...AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.展开更多
Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceU...Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceUular permeability in submandibular glands. However, the molecular mechanisms underlying AMPK-modulated paraceUular permeability are unknown. In this study, we found that AICAR, an AMPK agonist, increased saliva secretion in the isolated rat submandibular glands, decreased transepithelial electrical resistance （TER）, and increased 4 kDa FITC-dextran flux in cultured SMG-C6 cells. AICAR also induced redistribution of tight junction protein claudin-4, but not claudin-1, claudin-3, occtudin, or ZO-1, from the cytoplasm to the membrane. Moreover, knockdown of claudin-4 by shRNA suppressed while claudin-4 re-expression restored the TER and 4 kDa FITC-dextran flux responses to AICAR. Additionally, AICAR increased ERK1/2 phosphorylation, and inhibition of ERK1/2 by U0126, an ERK1/2 kinase inhibitor, or by siRNA decreased AICAR-induced TER responses. AICAR induced the serine S199 phosphorylation of claudin-4 and enhanced the inter- action of claudin-4 and occludin. Furthermore, pretreatment with U0126 significantly suppressed AMPK-modulated phosphorytation, redistribution, and interaction with occludin of claudin-4. Taken together, these results indicated that claudin-4 played a crucial role in AMPK-rnodutated paraceUular permeability and ERK1/2 was required in AMPK-modulated tight junction barrier function in subman- dibular gland.展开更多
基金Supported by Cooperation survey and research project of the Nippon Foundation of the Japan-China Medical Association (2006-12)the International cooperation project (BZ2006058) of Bureau of Science and Technology of Jiangsu Province,China
文摘AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.
文摘Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceUular permeability in submandibular glands. However, the molecular mechanisms underlying AMPK-modulated paraceUular permeability are unknown. In this study, we found that AICAR, an AMPK agonist, increased saliva secretion in the isolated rat submandibular glands, decreased transepithelial electrical resistance （TER）, and increased 4 kDa FITC-dextran flux in cultured SMG-C6 cells. AICAR also induced redistribution of tight junction protein claudin-4, but not claudin-1, claudin-3, occtudin, or ZO-1, from the cytoplasm to the membrane. Moreover, knockdown of claudin-4 by shRNA suppressed while claudin-4 re-expression restored the TER and 4 kDa FITC-dextran flux responses to AICAR. Additionally, AICAR increased ERK1/2 phosphorylation, and inhibition of ERK1/2 by U0126, an ERK1/2 kinase inhibitor, or by siRNA decreased AICAR-induced TER responses. AICAR induced the serine S199 phosphorylation of claudin-4 and enhanced the inter- action of claudin-4 and occludin. Furthermore, pretreatment with U0126 significantly suppressed AMPK-modulated phosphorytation, redistribution, and interaction with occludin of claudin-4. Taken together, these results indicated that claudin-4 played a crucial role in AMPK-rnodutated paraceUular permeability and ERK1/2 was required in AMPK-modulated tight junction barrier function in subman- dibular gland.
