Rat pancreas secretes particulate ecto-nucleotidase CD39

Area of Science:

• Cell Biology
• Gastroenterology
• Biochemistry

Background:

• Pancreatic acini release ATP, which may act as a paracrine regulator between acini and ducts.
• Purinergic receptors on pancreatic ducts suggest a role for ATP in acinar-ductal signaling.
• The regulation of this signaling by nucleotidases in the pancreas is not well understood.

Purpose of the Study:

• To investigate if nucleotidases regulate acinar-ductal signaling in the rat pancreas.
• To characterize and localize ecto-nucleoside triphosphate diphosphohydrolase, CD39, in the pancreas.

Main Methods:

• Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect CD39 expression.
• Immunofluorescence microscopy localized CD39 within pancreatic tissues and secretions.
• Nucleotidase activity in pancreatic juice was measured after stimulation with cholecystokinin-octapeptide-8 (CCK-8) and secretin.

Main Results:

• The full-length ecto-nucleoside triphosphate diphosphohydrolase, CD39, is expressed in the rat pancreas.
• CD39 is localized on acinar basolateral membranes and ductal membranes (luminal in small ducts, basolateral in large ducts).
• CCK-8 stimulation induces relocalization and secretion of particulate CD39 into pancreatic juice, reducing ATP levels.
• Secretin stimulation did not result in detectable CD39 activity in secretions.

Conclusions:

• A novel, inducible release of full-length particulate CD39 from pancreatic acini occurs upon CCK-8 stimulation.
• Secreted CD39 likely regulates intraluminal ATP concentrations within the pancreatic ductal tree.
• This mechanism represents a new form of physiological acinar-ductal signaling in the pancreas.