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Effects of Phenylephrine on Transplanted Submandibular Gland

¹ Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Zhong Guan Cun South St. 22, 100081, Beijing, PRC;
² Department of Physiology and Pathophysiology, Peking University Health Science Center, 100083, Beijing;
³ Dalian Medical University School of Stomatology, 116011, Dalian; and
⁴ Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, 100083, Beijing

^* co-corresponding authors, gyyu{at}263.net and pathophy{at}bjmu.edu.cn

	ABSTRACT

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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 _1A-, _1B-, and _1D-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-PKC, and PKC in the transplanted gland. These results indicate that phenylephrine treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through promoting ₁-adrenoceptor expression and post-receptor signal transduction.

KEY WORDS: submandibular gland auto-transplantation • ₁-adrenoceptor • phenylephrine

	INTRODUCTION

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Keratoconjunctivitis sicca is a disease characterized by reduction or lack of tears, with serious complications. Despite the generally efficient pharmaceutical tear substitutes, tarsorrhaphy, or occlusion of the tear drainage system, individuals severely affected did not gain adequate relief of discomfort and often experienced corneal changes (Sieg et al., 2000). Autotransplantation of the submandibular gland is one of the effective approaches for treating severe keratoconjunctivitis sicca (Murube-Del-Castillo, 1986; Geerling et al., 1998; Sieg et al., 2000; Yu et al., 2004). However, almost all individuals experience a post-operative reduction of secretion of the transplanted glands from 5 days to 3 mos, which may lead to obstruction of Wharton’s duct, or even to failure of the transplantation (Yu et al., 2004). Therefore, if the success rate of transplantation is to be increased, it is critical that the secretion of transplanted glands be improved in the early post-operative stage.

It is well-known that the activation of cholinergic receptors and -adrenoceptors is the main stimulus for fluid secretion, while ß-adrenoceptor stimulation causes protein secretion in submandibular glands (Castle and Castle, 1996; Baum and Wellner, 1999). Since secretion of transplanted glands could be increased by physical activity, massage, and hot compresses instead of by food ingestion, we speculated that the increased secretion in the transplanted gland might be derived from adrenoceptor activation. Expressions of _1A-, _1B-, and _1D- adrenoceptor mRNAs were detected in rat and rabbit submandibular glands (Piao et al., 2000; Bockman et al., 2004). Activation of ₁-adrenoceptor by sympathetic neurotransmitters has been found to evoke salivary fluid secretion in both innervated and denervated rat submandibular glands (Bylund et al., 1982; Elverdin et al., 1984; Baum and Wellner, 1999). Zhu et al. utilized a rabbit model to examine the morphological changes in autotransplanted submandibular glands (Zhu et al., 2002). They found that there were atrophic changes in secretory cells within 60 days after transplantation (Zhu et al., 2001). However, the regulation of the secretion of denervated transplanted submandibular glands remains unclear. In this study, we investigated whether phenylephrine could affect the structure and function of the autotransplanted submandibular gland in rabbits.

	MATERIALS & METHODS

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Experimental Animals
Healthy male New Zealand white rabbits, weighing 2.4 ± 0.3 kg each, were used. All experimental procedures were in accordance with the Guidance of the Chinese Ministry of Public Health for the care and use of laboratory animals.

Reagents and Antibodies
Phenylephrine was purchased from Sigma (St. Louis, MO, USA). Antibodies to aquaporin-5 (AQP5), proliferating cell nuclear antigen (PCNA), protein kinase C (PKC) and phospho-PKC, extracellular signal-regulated kinase (ERK1/2) and phospho-ERK1/2, and FITC-conjugated secondary antibody were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibody to actin was purchased from Oncogene (Cambridge, MA, USA).

Experimental Groups and Operative Technique
With the rabbit under sodium pentobarbital (20 mg/kg body wt) anesthesia, its right submandibular gland, with the Wharton’s duct and related blood vessels, was isolated from the submaxillary triangle. The freed gland was transplanted to the left temporal region and revascularized by anastomosis of the artery of the gland to the distal part of the external carotid artery, and the vein of the gland to the temporal vein. A polyethylene tube was inserted into the Wharton’s duct and left outside the temporal skin. Rabbits were randomly divided into 3 groups: control (without transplantation), transplanted, and phenylephrine (transplantation with phenylephrine treatment). Phenylephrine (10^–7 mol/L, 100 µL) or normal saline (100 µL) was slowly infused into the Wharton’s duct from post-operative days 1–7, while the animals were conscious. On post-operative day 7, glands were removed under anesthesia.

Measurement of Salivary Secretion
Five min after phenylephrine or saline perfusion, salivary flow was measured for 5 min, on post-operative days 1–7, by the insertion of a piece of moist filter paper (35 mm x 5 mm) through the cannula inserted into the Wharton’s duct. All collections were made between 9:30 a.m. and 10:30 a.m. from the resting and conscious animals. Saliva collected from post-operative days 1–7 was pooled for biochemical analysis of the concentrations of electrolytes and the activity of -amylase.

Reverse-transcriptase Polymerase Chain-reaction (RT-PCR)
Total RNA was purified with Trizol (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. cDNA was prepared from 5 µg of total RNA with M-MLV reverse-transcriptase (Promega, Madison, WI, USA). The primers for ₁-adrenoceptor subtypes (Table) were designed and synthesized (AoKe Biotech, Beijing, PRC) based on the mRNA sequence of rabbit _1A-, _1B-, and _1D-adrenoceptor (GenBank-U81982, AF156106, and U64032). Amplification of ß-actin was performed for internal standardization. DEPC H₂O instead of RT product and human ₁-adrenoceptor subtype full-length cDNA were amplified as negative and positive controls, respectively. The band densities were quantitated by the use of a gel electrophoresis image system.

View this table: [in this window] [in a new window]   Table. Primers for Rabbit 1-Adrenoceptor Subtype mRNA

Light Microscopic and Transmission Electron Microscopic Observations
The submandibular gland sections were stained with hematoxylineosin so that morphologic changes could be evaluated by light microscopy. Specimens were fixed in 2% paraformaldehyde-1.25% glutaraldehyde for evaluation by transmission electron microscopy (TEM). Ultrathin sections were stained with uranyl acetate and lead citrate, and observed with a TEM (H-7000 electron microscope; HITA-CHI, Tokyo, Japan).

Immunohistochemical Staining
The submandibular glands were immunostained with goat polyclonal antibody against PCNA (1:100), by routine immunohistochemistry. Negative controls were incubated with goat IgG replacing the primary antibody. The PCNA-positive cells were counted in 10 different fields in each section under 400x magnification.

Western Blot Analysis
Equal amounts of protein from different groups were separated on 12% SDS-PAGE, electrotransferred to polyvinylidene difluoride membrane, and probed with primary antibodies and horseradish peroxidase-conjugated secondary antibodies and chemiluminescence. Filters were re-probed with antibody against actin after being stripped to ensure equal loading of the lanes.

Statistical Analysis
Data are expressed as means ± SEM. Comparison of means was performed by one-way analysis of variance (ANOVA), followed by Bonferroni’s tests. Values of P < 0.05 were considered statistically significant.

	RESULTS

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Saliva Flow Rate and Composition in Submandibular Glands
To evaluate the salivary flow rate and composition of the transplanted glands in the early phase, we collected saliva directly from the cannula inserted into the transplanted glands. The saliva secreted from transplanted glands was increased on post-operative day 1, decreased on post-operative day 3, and hardly detectable on post-operative days 4–7 (Fig. 1A). To avoid the effects of phenylephrine via vein administration on the cardiovascular system, we administered it to the transplanted glands through the cannula. In the preliminary experiments, 10^–7 mol/L of phenylephrine (100 µL) effectively stimulated salivary secretion without inducing vasoconstriction in submandibular glands, monitored by a Laser Doppler instrument. The blood pressure and heart rate of rabbits were unchanged under this dosage (data not shown). Treatment with phenylephrine markedly increased the secretion from transplanted glands from post-operative days 1–7. The -amylase activity and concentrations of sodium and potassium in saliva collected from transplanted glands were higher than those in the control group. After phenylephrine treatment, the concentration of sodium was significantly decreased to control levels, while the -amylase activity and the concentration of potassium remained higher compared with the controls (Figs. 1B, 1C, 1D).

View larger version (87K): [in this window] [in a new window]   Figure 1. Effects of phenylephrine on salivary secretion, mRNA expressions of 1-adrenoceptor subtypes, and localization of AQP5 in transplanted glands. Salivary flow (A), activity of -amylase (B), sodium concentration (C), and potassium concentration (D) of the saliva were measured as described in MATERIALS & METHODS. The transplanted glands were administrated phenylephrine from post-operative day 1. The expressions of 1A-, 1B-, and 1D-adrenoceptor mRNA were detected by RT-PCR in control, transplanted, and phenylephrine-treated glands (n = 6) (E,F,G). All values are given as means ± SEM. N, control submandibular gland; T, transplanted gland; T + PE, transplanted gland with phenylephrine treatment. *P < 0.05 and **P < 0.01 compared with N; #P < 0.05 compared with T. The reactivity to anti-AQP5 antibody was detected with FITC-conjugated secondary antibody. Sections were examined by confocal microscopy. (H) Control submandibular gland. AQP5 was located in both the apical membrane and the cytoplasm. (I) Transplanted gland. AQP5 was diffused in cytoplasm. (J) Translocation of AQP5 from cytoplasm to the apical membrane in phenylephrine-treated gland. Bars (H,I,J): 20 µm.

Expression of ₁-Adrenoceptor Subtype mRNA in the Submandibular Gland

Effect of Phenylephrine on AQP5 Translocation
AQP5 was localized in both the apical membrane and the cytoplasm under unstimulated conditions (Fig. 1H). AQP5 was dispersed in the cytoplasm in transplanted glands on post-operative day 7 (Fig. 1I). After phenylephrine treatment, AQP5 was translocated from the cytoplasm to the apical membrane (Fig. 1J).

Histologic and Ultrastructural Changes in Transplanted Glands
Normal acinar and ductal cells in control submandibular glands were displayed by light microscopy (Fig. 2A). Acinar cells in transplanted glands were shown to atrophy, compared with controls, on post-operative day 7 (Fig. 2B). After phenylephrine treatment for 7 days, the glandular atrophy was ameliorated, and its morphologic manifestation was much closer to that of the control (Fig. 2C). The acinar cells in control submandibular glands contained many low-matrix-density secretory granules in the cytoplasm, under TEM (Fig. 2D), but there were fewer in transplanted glands on post-operative day 7 compared with the controls (Fig. 2E). In the phenylephrine-treated glands, abundant low-density secretory granules were observed in acinar cells, and their sizes were similar to those seen in the cells in the control glands (Fig. 2F).

View larger version (204K): [in this window] [in a new window]   Figure 2. The histologic structure and ultrastructure of transplanted submandibular glands. All submandibular gland tissues were removed on post-operative day 7. (A) Histologic structure of a control submandibular gland. An acinar cell is indicated by an arrow. (B) Histologic structure of transplanted gland. Acinar cells show size reduction (arrow). (C) Histologic structure of phenylephrine-treated gland. Acinar cells show only mild size reduction (arrow). Light microscopy, magnification 400x. Bars (A,B,C): 20 µm. (D) Ultrastructure of control submandibular gland. Low-matrix-density secretory granule in acinar cell is indicated by an arrow. (E) Ultrastructure of transplanted submandibular gland. The low-matrix-density secretory granules (arrow) were decreased as compared with those in the control submandibular gland. (F) Ultrastructure of phenylephrine-treated gland. The low-density secretory granules (arrow) are similar to those in the control submandibular gland. TEM magnification, 5000x. Bars (D,E,F): 2 µm.

View larger version (83K): [in this window] [in a new window]   Figure 3. Alterations of PCNA and MAPK signal pathways in transplanted submandibular glands. Immunohistochemical localizations of PCNA in control submandibular gland (A), transplanted gland (B), and phenylephrine-treated gland (C) are shown. PCNA-positive cell is indicated by an arrow. Light microscopy, magnification 400x. Bars (A,B,C): 20 µm. (D) Semiquantitative scoring of PCNA-positive cells (n = 6). The PCNA-positive cells were counted in 10 different fields in each section (1 section/each animal) under 400x magnification. (E) Western blot analysis of phospho-PKC and PKC. An 80-µg quantity of protein was separated by 12% SDS-polyacrylamide gel electrophoresis and immunoblotted either with an antibody specific for phospho-PKC or for total PKC. (F) Western blot analysis of phospho-ERK1/2 and ERK1/2. An 80-µg quantity of protein was separated by 12% SDS-polyacrylamide gel electrophoresis and immunoblotted either with an antibody specific for phospho-ERK1/2 or for total ERK1/2. Filters were re-probed with antibody against actin to ensure equal loading of the lanes. The blot is a representative of 5 separated animals in each group, with similar results. All values are given as means ± SEM. N, control submandibular gland; T, transplanted gland; T + PE, transplanted gland with phenylephrine treatment. *P < 0.05 and **P < 0.01 compared with N; #P < 0.05 and ##P < 0.01 compared with T.

Effects of PE on PKC and ERK1/2 Protein Expression in Submandibular Glands

	DISCUSSION

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Earlier studies have reported that parasympathetic and sympathetic denervation of the rabbit submandibular gland caused atrophy of the acinar cells (Kyriacou and Garrett, 1998). In this study, we demonstrated that the atrophy of the acinar cells, in addition to a decrease in secretion, is an early morphological change in transplanted glands. Phenylephrine treatment could improve secretion and ameliorate the atrophy of the transplanted glands in the early phase after transplantation. It is well-known that denervation induces "super-sensitivity secretion" and "degeneration secretion" in salivary glands, due to the release of neurotransmitters from the degenerating nerves during the early stages after denervation (Delfs and Emmelin, 1974; for review, see Proctor, 1999). Consistent with these early observations, our clinical studies also found that salivary flow was increased soon post-operatively and decreased on post-operative day 5 in transplanted glands (Yu et al., 2004). Our results indicate that the administration of phenylephrine might aid in the prevention of ductal obstruction after transplantation by stimulating secretion.

In agreement with our previous clinical observations in human submandibular gland transplantation (Li et al., 2002), we found that the K⁺ concentration was significantly increased, while the Na⁺ concentration and -amylase activity were slightly increased in transplanted rabbit submandibular glands. It has been well-established that the primary saliva secreted from acini is a plasma-like fluid, with high concentrations of Na⁺ and low levels of K⁺. When saliva flows through the duct system, its composition is greatly modified by ductal cells through re-absorption of Na⁺ and Cl^– and release of K⁺ and HCO₃^–. Stimulation of adrenergic or cholinergic receptors activates these ion transporters in ductal cells. The increase in K⁺ concentration in the saliva from transplanted glands, as observed in our studies, indicates that the ductal cells in these glands were activated by transplantation. The amylase increase was likely due to up-regulated acinar secretion of the protein in transplanted glands. Interestingly, phenylephrine did not further increase K⁺ levels. These observations may result from the activation of the cells in transplanted glands, due to the "degeneration secretion" of the neurotransmitters in the early stage after transplantation. Further stimulation of the cells with phenylephrine failed to trigger any additional response. The accurate underlying mechanisms mediating these changes are currently under further investigation.

Little is known about alterations in ₁-adrenoceptor subtypes in the transplanted organs. We found that mRNAs of 3 subtypes of ₁-adrenoceptors, especially _1A- and _1D-adrenoceptors, were elevated in transplanted glands and further increased in phenylephrine-treated glands. Therefore, transcriptional induction of ₁-adrenoceptors could be a potential mechanism for sustained secretion, a chronic response to catecholamine in transplanted glands.

It is known that the activation of ₁-adrenoceptors plays an important role in regulating cell growth and proliferation through mitogen-activated protein kinase (MAPK) pathways (Alexandrov et al., 1998; Lazou et al., 1998). Enhanced cell proliferation after ischemia is considered a sign of initiation of regeneration of the gland tissue (Sieg et al., 2000). In the present study, PCNA-positive cells were identified in transplanted glands and markedly increased in phenylephrine-treated glands. This suggests that the regenerative capacity of transplanted glands could be enhanced by phenylephrine. ₁-Adrenoceptor can activate MAPK through the G_q/PKC/Raf-1-dependent pathway (Post and Brown, 1996). PKC, an atypical PKC, has been implicated in the suppression of apoptosis, is required for ERK activation, and mediates the proliferation of a plethora of cell types (for review, see Hennige et al., 2002; Gutcher et al., 2003; Muscella et al., 2003; Parmentier et al., 2003). Importantly, we found that phenylephrine significantly increased the levels of phosphorylated PKC and ERK1/2 in transplanted glands. These results indicate that the activation of ₁-adrenoceptor by phenylephrine can promote the regeneration of transplanted glands by activating the MAPK signal pathway.

Moreover, localization of AQP5 may be critical to its function in salivary fluid secretion (for review, see Melvin et al., 2005). Interestingly, our studies demonstrated that the activation of the ₁-adrenoceptor by phenylephrine could induce translocation of AQP5 from the cytoplasm to the apical membrane. The results suggest that the increased salivary secretion stimulated by phenylephrine may be mediated by the translocation of AQP5 in transplanted glands. In support of our observation, phenylephrine was found to induce the trafficking of AQP5 to the apical membrane in rat parotid cells (Ishikawa et al., 1999).

In summary, our studies demonstrated that phenylephrine stimulated salivary secretion, ₁-adrenoceptor subtype mRNA up-regulation, and AQP5 translocation in transplanted glands. Phenylephrine also ameliorated atrophy and may promote cell proliferation in transplanted glands by activating PKC and ERK1/2. Our results suggest that phenylephrine has the potential to be used for clinical prevention of the reduction of secretion of submandibular glands during the early phase of transplantation.

	ACKNOWLEDGMENTS

 
This study was supported by grants from the National Nature Science Foundation of China (Nos. 30171016 and 30371545), the Ministry of Education (No. 104002), the Ministry of Science and Technology (No. 2003CCC00800), and the Program for Changjiang Scholars and Innovative Research Team in University. The authors thank Professor Cun-yu Wang at the University of Michigan School of Dentistry and Medicine, and Dr. Guo H. Zhang at the National Center for Research Resources, National Institutes of Health, USA, for reviewing the manuscript.

Received January 15, 2006; Last revision July 8, 2006; Accepted September 5, 2006

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
Alexandrov A, Keffel S, Goepel M, Michel MC (1998). Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase. Mol Pharmacol 54:755–760.[Abstract/Free Full Text]

Baum BJ, Wellner RB (1999). Receptors in salivary glands. In: Neural mechanisms of salivary gland secretion. Garrett JR, Ekström J, Anderson LC, editors. Frontiers of Oral Biology. Basel: Karger, pp. 44–58.

Bockman CS, Bruchas MR, Zeng W, O’Connell KA, Abel PW, Scofield MA, et al. (2004). Submandibular gland acinar cells express multiple alpha1-adrenoceptor subtypes. J Pharmacol Exp Ther 311:364–372.[Abstract/Free Full Text]

Bylund DB, Martinez JR, Pierce DL (1982). Regulation of autonomic receptors in rat submandibular gland. Mol Pharmacol 21:27–35.[Abstract]

Castle JD, Castle AM (1996). Two regulated secretory pathways for newly synthesized parotid salivary proteins are distinguished by doses of secretagogues. J Cell Sci 109(Pt 10):2591–2599.[Abstract]

Delfs U, Emmelin N (1974). Degeneration secretion of saliva in the rat following sympathectomy. J Physiol 239:623–630.[Abstract/Free Full Text]

Elverdin JC, Luchelli-Fortis MA, Stefano FJ, Perec CJ (1984). Alpha-1 adrenoceptors mediate secretory responses to norepinephrine in innervated and denervated rat submaxillary glands. J Pharmacol Exp Ther 229:261–266.[Abstract/Free Full Text]

Geerling G, Sieg P, Bastian GO, Laqua H (1998). Transplantation of the autologous submandibular gland for most severe cases of keratoconjunctivitis sicca. Ophthalmology 105:327–335.[ISI][Medline]

Gutcher I, Webb PR, Anderson NG (2003). The isoform-specific regulation of apoptosis by protein kinase C. Cell Mol Life Sci 60:1061–1070.[ISI][Medline]

Hennige AM, Fritsche A, Strack V, Weigert C, Mischak H, Borboni P, et al. (2002). PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046–38. Biochem Biophys Res Commun 290:85–90.[ISI][Medline]

Ishikawa Y, Skowronski MT, Inoue N, Ishida H (1999). Alpha(1)-adrenoceptor-induced trafficking of aquaporin-5 to the apical plasma membrane of rat parotid cells. Biochem Biophys Res Commun 265:94–100.[ISI][Medline]

Ishikawa Y, Yuan Z, Inoue N, Skowronski MT, Nakae Y, Shono M, et al. (2005). Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland. Am J Physiol Cell Physiol 289:C1303–C1311.[Abstract/Free Full Text]

Kyriacou K, Garrett JR (1988). Morphological changes in the rabbit submandibular gland after parasympathetic or sympathetic denervation. Arch Oral Biol 33:281–290.[ISI][Medline]

Lazou A, Sugden PH, Clerk A (1998). Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart. Biochem J 332(Pt 2):459–465.[ISI][Medline]

Li XX, Zhu ZH, Yu GY, Zhang L, Peng KF (2002). Analysis of tears components in submaxillary gland autotransplanted patients with kerato-conjunctivitis. J Modern Stomatol 16:240–242 [article in Chinese].

Melvin JE, Yule D, Shuttleworth T, Begenisich T (2005). Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol 67:445–469.[ISI][Medline]

Murube-Del-Castillo J (1986). Transplantation of salivary gland to the lacrimal basin. Scand J Rheumatol Suppl 61:264–267.[Medline]

Muscella A, Greco S, Giovanna E, Storelli C, Marsigliante S (2003). PKC-zeta is required for angiotensin II-induced activation of ERK and synthesis of C-FOS in MCF-7 cells. J Cell Physiol 197:61–68.[ISI][Medline]

Parmentier JH, Smelcer P, Pavicevic Z, Basic E, Idrizovic A, Estes A, et al. (2003). PKC-zeta mediates norepinephrine-induced phospholipase D activation and cell proliferation in VSMC. Hypertension 41(3 Pt 2):794–800.[Abstract/Free Full Text]

Piao H, Taniguchi T, Nakamura S, Zhu J, Suzuki F, Mikami D, et al. (2000). Cloning of rabbit alpha(1b)-adrenoceptor and pharmacological comparison of alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptors in rabbit. Eur J Pharmacol 396:9–17.[ISI][Medline]

Post GR, Brown JH (1996). G protein-coupled receptors and signaling pathways regulating growth responses. FASEB J 10:741–749.[Abstract]

Proctor GB (1999). Effects of automatic denervations on protein secretion and synthesis by salivary glands. In: Neural mechanisms of salivary gland secretion. Frontiers of Oral Physiology. Garrett JR, Ekstrom J, Anderson LC, editors. Basel: Karger, pp. 150–165.

Sieg P, Geerling G, Kosmehl H, Lauer I, Warnecke K, von Domarus H (2000). Microvascular submandibular gland transfer for severe cases of keratoconjunctivitis sicca. Plast Reconstr Surg 106:554–560.[ISI][Medline]

Yu GY, Zhu ZH, Mao C, Cai ZG, Zou LH, Lu L, et al. (2004). Microvascular autologous submandibular gland transfer in severe cases of keratoconjunctivitis sicca. Int J Oral Maxillofac Surg 33:235–239.[ISI][Medline]

Zhu ZH, Yu GY, Zou LH, Liu DG, Sun KH, Wu DC (2002). The pathological changes of the denervated gland after vascularized autologous submandibular gland transfer. J Peking Univ (Health Sci) 34:108–111 [article in Chinese].

This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xiang, B. Articles by Yu, G.Y. Search for Related Content PubMed PubMed Citation Articles by Xiang, B. Articles by Yu, G.Y.