Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands.
Summary of "Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands."
The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7-/- (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7-/- mice; and in contrast, tear secretion was increased in P2X7-/- mice. The secretory phenotype was also dependent on the gender of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X7 receptor and the gender of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptors signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion.
Affiliation
University of Copenhagen.
Journal Details
This article was published in the following journal.
Name: The Journal of physiology
ISSN: 1469-7793
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20643770
- DOI: http://dx.doi.org/10.1113/jphysiol.2010.190017
Medical and Biotech [MESH] Definitions
Pancreas, Exocrine
The major component (about 80%) of the PANCREAS composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as TRYPSINOGEN; LIPASE; AMYLASE; and RIBONUCLEASE. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the DUODENUM.
Exocrine Pancreatic Insufficiency
A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes (LIPASE; PROTEASES; and AMYLASE) by the EXOCRINE PANCREAS into the DUODENUM. This condition is often associated with CYSTIC FIBROSIS and with chronic PANCREATITIS.
Pancreas
A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
Pancreatic Function Tests
Tests based on the biochemistry and physiology of the exocrine pancreas and involving analysis of blood, duodenal contents, feces, or urine for products of pancreatic secretion.
Receptor, Cholecystokinin A
A subtype of cholecystokinin receptor found primarily in the PANCREAS; STOMACH; INTESTINE; and GALLBLADDER. It plays a role in regulating digestive functions such as gallbladder contraction, pancreatic enzyme secretion and absorption in the GASTROINTESTINAL TRACT.
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