Phenylephrine Improves Function of Autotransplanted Submandibular Gland in Rabbit

Objective: Microvascular autotransplantation of submandibular gland(SMG) is one of the most effective treatments for severe keratoconjunctivitis sicca. However, secretion of the transplanted gland decreases during the first 3 months after operation, which may lead to obstruction of Wharton's duct, or even failure of the transplantation. The purpose of this study was to investigate the effect of phenylephrine(PE), an agonist of a1-adrenoceptor(a1-AR) on transplanted SMG in rabbit. Methods: SMG autotransplantation was performed and PE(0.1µmol/L, 100µl) was infused into the Wharton's duct from postoperative day (POD) 1 to 7. Salivary flow was measured by the length of moist filter paper. Expression of a1-AR subtype mRNA was measured by RT-PCR. The location of aqauporin5(AQP5) was identified by confocal microscopy. Morphologic changes of SMG were observed by light microscopy and transmission electron microscopy. Expressions of proliferating cell nuclear antigen(PCNA), protein kinase C z(PKCz) and extracellular signal-regulated kinase(ERK1/2) were determined by Western blot. Results: Salivary secretion decreased after transplantation, whereas significantly increased by phenylephrine treatment for 7 days. Expressions of a1A-, a1B-, and a1D-AR mRNA were elevated in transplanted SMG and further increased in phenylephrine group. Phenylephrine promoted AQP5 translocation from cytoplasm to the apical membrane, ameliorated atrophy of acinar cells, and increased PCNA-positive cells in transplanted SMG. Expressions of phospho-ERK1/2, ERK1/2, phospho-PKCz, and PKCz were elevated in transplanted gland and further increased in phenylephrine group. Conclusions: The results suggest that therapy with phenylephrine attenuates structural injury and improves secretory function in transplanted SMG. The protective mechanism of phenylephrine may involve in a1-adrenoceptor mRNA upregulation and postreceptor signal activation.