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) produces a pronounced atrophy that is reversed upon ligatureremoval. Based on previous studies by our group and others suggestingthat P2Y₂ nucleotide receptors are upregulated in response to tissue damage, we hypothesized that P2Y₂ receptoractivity and mRNA levels would increase after duct ligation and return to control levels after ligature removal. Our results support thishypothesis. Intracellular Ca²⁺ mobilization in response tothe P2Y₂ receptor agonist UTP in SMG cells was increasedsignificantly after ligation periods of 1.5 to 7 days, whereas nosignificant response was observed in the contralateral, nonligatedgland. P2Y₂ receptor mRNA, as measured bysemiquantitative RT-PCR, increased about 15-fold after 3 days ofligation. These increases reverted to control levels by 14 days afterligature removal. In situ hybridization revealed that the changes inP2Y₂ receptor mRNA abundance occurred mostly in acinarcells, which also were more adversely affected by ligation, includingan increase in the appearance of apoptotic bodies. These findingssupport the idea that P2Y₂ receptor upregulation may be animportant component of the response to injury in SMG and that recoveryof normal physiological function may signal a decreased requirement forP2Y₂ receptors.