Effects of Phenylephrine on Transplanted Submandibular Gland

Abstract

Autotransplantation of the submandibular gland is a potential treatment for severe kerato-conjunctivitis sicca. However, one of the major barriers to this procedure is that secretions from the transplanted gland decrease shortly after the operation, which may lead to obstruction of Wharton's duct, or even to transplantation failure. Using a rabbit model, we investigated whether phenylephrine could improve the secretion from the transplanted gland. We found that phenylephrine treatment significantly reversed the decrease in salivary secretion after transplantation, enhanced the expressions of alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNA, and ameliorated atrophy of acinar cells. Furthermore, phenylephrine also induced translocation of aquaporin-5 from the cytoplasm to the apical membrane, and increased the levels of phospho-ERK1/2, ERK1/2, phospho-PKCzeta, and PKCzeta in the transplanted gland. These results indicate that phenylephrine treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through promoting alpha1-adrenoceptor expression and post-receptor signal transduction.

Activation of transient receptor potential vanilloid subtype 1 increases expression and permeability of tight junction in normal and hyposecretory submandibular gland

“…21 Briefly, under sodium pentobarbital (20 mg/kg, in ear vein) anesthesia, the right SMG with its Wharton's duct and related blood vessels were isolated from the submaxillary triangle to the left temporal region. The artery of the gland was revascularized to the distal part of the external carotid artery, and the vein to the temporal vein.…”

Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland

“…Our previous experiments showed that a lack of transmitter support was involved in the early hyposecretion, and local supplementation with phenylephrine or isoproterenol from Wharton's duct improved secretion of the transplanted gland early after surgery (17,38). However, systemic administration of exogenous adrenergic agonists may induce a wide range of pharmacological effects, especially for patients with cardiovascular disease, and local perfusion from Wharton's duct is not convenient.…”

“…The autotransplantation was performed as previously described (38). Briefly, anesthesia was induced by an intravenous injection of pentobarbital sodium (20 mg/kg).…”

“…Decreased expression of AQP5 is common in salivary gland hypofunction induced by radiation therapy (18,32). Our previous results showed that the expression of AQP5 was reduced and dispersed in the cytoplasm of acini in transplanted glands on postoperative day 7 (38). Thus the identification of molecular mechanisms regulating the activity of AQP5 in the submandibular gland will provide further understanding of the pathophysiological mechanisms of salivary dysfunction and useful insights into novel antihyposecretion therapies.…”

Interleukin 1β attenuates vascular α1 adrenergic receptors expression following lipopolysaccharide-induced endotoxemia in rabbits

“…Complementary DNAwas prepared from 1 Hg of total RNAwith Reverse Transcription System (Promega, San Luis Obispo, CA). The primers for three isoforms of > 1 AR and A-actin were designed according to the literature 26,27 and were synthesized in Invitrogen Company. Amplification of A-actin was performed for internal standardization.…”