Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx.
Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca(2+)-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca(2+)-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca(2+) entry into primary LES cells in addition to intracellular Ca(2+) release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca(2+) influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca(2+) influx pathway.
School of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City 807, Taiwan. u101130@yahoo.com.tw.|Departments of Pediatrics, E-Da Hospital, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. u101130@yahoo.com.tw.
Ching-Chung
CC
Tsai
Department of Occupational Therapy, I-Shou University, No. 8, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. changlc@isu.edu.tw.|Department of Pharmacy, E-Da Hospital, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. changlc@isu.edu.tw.
Li-Ching
LC
Chang
Department of Internal Medicine, E-Da Hospital, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. shihchehuang@hotmail.com.|School of Medicine, I-Shou University, No. 8, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 824, Taiwan. shihchehuang@hotmail.com.
Shih-Che
SC
Huang
Departments of Pediatrics, E-Da Hospital, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. djsr2000@hotmail.com.
Shu-Leei
SL
Tey
Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, No. 1, Dasyue Road, East District, Tainan City 701, Taiwan. hsuwenli0626@gmail.com.
Wen-Li
WL
Hsu
Departments of Pediatrics, E-Da Hospital, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 824, Taiwan. suyutsun@yahoo.com.tw.
Yu-Tsun
YT
Su
School of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City 807, Taiwan. fruit0227@hotmail.com.
Ching-Wen
CW
Liu
School of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City 807, Taiwan. trtsai@kmu.edu.tw.
Tong-Rong
TR
Tsai
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*
D002121:Calcium Channel Blockers; D010936:Plant Extracts; D044169:Receptors, Calcium-Sensing; D002118:Calcium
Salvia miltiorrhiza; lower esophageal sphincter; tonic contraction