Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.
OBJECTIVE
To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats).


METHODS
After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels.


RESULTS
Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin.


CONCLUSIONS
Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.
LeSagE
G
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Department of Internal Medicine, Scott & White Hospital, and Texas A&M University System Health Science Center College of Medicine, Temple, Texas, USA.
Alvaro
D
D
Benedetti
A
A
Glaser
S
S
Marucci
L
L
Baiocchi
L
L
Eisel
W
W
Caligiuri
A
A
Phinizy
J L
JL
Rodgers
R
R
Francis
H
H
Alpini
G
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001652:Bile Ducts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D006728:Hormones / Q000097:blood; D008026:Ligation; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011950:Receptors, Cholinergic / Q000378:metabolism; D014628:Vagotomy
D006728:Hormones; D011950:Receptors, Cholinergic; D005576:Colforsin; D000242:Cyclic AMP