Reversible regulation of P2Y(2) nucleotide receptor expression in the duct-ligated rat submandibular gland

Ligation of the main excretory duct of the rat submandibular gland (SMG) pr oduces a pronounced atrophy that is reversed upon ligature removal. Based o n previous studies by our group and others suggesting that P2Y(2) nucleotid e receptors are upregulated in response to tissue damage, we hypothesized t hat P2Y(2) receptor activity and mRNA levels would increase after duct liga tion and return to control levels after ligature removal. Our results suppo rt this hypothesis. Intracellular Ca2+ mobilization in response to the P2Y( 2) receptor agonist UTP in SMG cells was increased significantly after liga tion periods of 1.5 to 7 days, whereas no significant response was observed in the contralateral, nonligated gland. P2Y(2) receptor mRNA, as measured by semiquantitative RT-PCR, increased about 15-fold after 3 days of ligatio n. These increases reverted to control levels by 14 days after ligature rem oval. In situ hybridization revealed that the changes in P2Y(2) receptor mR NA abundance occurred mostly in acinar cells, which also were more adversel y affected by ligation, including an increase in the appearance of apoptoti c bodies. These findings support the idea that P2Y(2) receptor upregulation may be an important component of the response to injury in SMG and that re covery of normal physiological function may signal a decreased requirement for P2Y(2) receptors.