Structure and function of the pancreas in the polycystic kidney rat.
OBJECTIVE
Mutation in the Pkhd1 gene that encodes a ciliary protein, fibrocystin, causes multiple cysts in the kidneys and liver in the polycystic kidney (PCK) rat, a model for human autosomal recessive PCK disease. To clarify the role of primary cilia in the pancreatic duct, we examined the structure and function of the exocrine pancreas of PCK rats.


METHODS
Pancreatic juice and bile were collected from anesthetized rats. Pancreatic ductal structure was analyzed by microdissection and immunohist0chemistry.


RESULTS
Histologically pancreatic acini were apparently normal, and no cysts were detected in the pancreas. Larger pancreatic ducts were irregularly dilated with enhanced expression of AQP1 in epithelial cells. The pancreatic duct of PCK rats exhibited significantly (P < 0.05) higher distensibility than that of wild-type (WT) rat at a physiological luminal pressure (3 cm H2O). Pancreatic fluid secretion stimulated with a physiological dose of secretin (0.03 nmol/kg per hour) in PCK rats was significantly smaller than that in WT, but the differences were not significant at higher doses. The amylase responses to carbamylcholine were not different between PCK and WT rats.


CONCLUSIONS
These findings suggest that fibrocystin/primary cilia-dependent mechanisms may play a role in the regulation of pancreatic ductal structure and fluid secretion.
Department of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Lanjuan
L
Yi
Satoru
S
Naruse
Sonoko
S
Furuya
Akiko
A
Yamamoto
Miyuki
M
Nakakuki
Shizuko
S
Nagao
Daisuke
D
Yoshihara
Shigeru B H
SB
Ko
Muxin
M
Wei
Takaharu
T
Kondo
Hiroshi
H
Ishiguro
D000681:Amylases / Q000378:metabolism; D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis; D001646:Bile / Q000187:drug effects; D002217:Carbachol / Q000008:administration & dosage; D018679:Cholinergic Agonists / Q000008:administration & dosage; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009154:Mutation; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D010183:Pancreatic Ducts / Q000473:pathology / Q000503:physiopathology; D010189:Pancreatic Juice / Q000187:drug effects / Q000502:physiology; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D012633:Secretin / Q000008:administration & dosage
C496022:Aqp1 protein, rat; D018679:Cholinergic Agonists; C479541:PKHD1 protein, rat; D011956:Receptors, Cell Surface; D012633:Secretin; D051398:Aquaporin 1; D002217:Carbachol; D000681:Amylases