Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation.
OBJECTIVE
To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs.


METHODS
SMG autotransplantation was performed in a rabbit model. Carbachol (1 microM) was infused into the transplanted glands from postoperative day 1-7. The expression of the M1 and M3 muscarinic receptors, aquaporin-5 (AQP5), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by RT-PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5-trisphosphate (IP(3)) was measured by radioimmunoassay.


RESULTS
Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP(3), p-ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells.


CONCLUSIONS
A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton's duct in the early phase after SMG transplantation.
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
L
L
Shi
X
X
Cong
Y
Y
Zhang
C
C
Ding
Q W
QW
Ding
F Y
FY
Fu
L L
LL
Wu
G Y
GY
Yu
D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D012463:Saliva / Q000187:drug effects* / Q000378:metabolism; D012472:Salivation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D014182:Transplantation, Autologous
D051402:Aquaporin 5; D018679:Cholinergic Agonists; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D002217:Carbachol