Shih-Che Huanga, b
a Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
b Department of Internal Medicine, School of Medicine, I-Shou University, Kaohsiung, Taiwan
Abstract
Objectives
The internal anal sphincter (IAS) plays an important role in maintaining continence. Atrial natriuretic peptide (ANP) could relax the IAS. The purpose of the present study was to investigate the roles of natriuretic peptide receptors (NPRs) in the IAS.
Materials and methods
Relaxation of isolated rat IAS strips caused by natriuretic peptides was measured using isometric transducers. Expression of NPRs was evaluated by reverse transcription–polymerase chain reaction (PCR), immunohistochemistry and real-time PCR.
Results
In the rat IAS, C-type natriuretic peptide (CNP) produced a marked and concentration-dependent relaxation while ANP caused a mild relaxation. By contrast, brain natriuretic peptide, dendroaspis natriuretic peptide, and des[Gln18, Ser19, Gly20, Leu21, Gly22]ANP(4–23) amide did not generate relaxation. CNP was much more effective than ANP and brain natriuretic peptide in stimulating the relaxation, indicating that NPR-B mediates IAS relaxation. The CNP-induced relaxation was inhibited by the protein kinase G inhibitor Rp-8CPT-cGMPS and potassium channel blocker charybdotoxin but not by protein kinase A inhibitor Rp-cAMPS. This suggests the involvement of cGMP and calcium-activated potassium channels in the CNP-induced IAS relaxation. Reverse transcription PCR and immunohistochemistry revealed the existence of NPR-B in the rat IAS. Furthermore, real-time PCR identified abundant expression of CNP and NPR-B in the rat IAS.
Conclusion
CNP causes relaxation of the IAS via NPR-B, cGMP, and potassium channel pathways in rats. CNP might regulate IAS motility. NPR-B is a potential therapeutic target in anorectal motility disorders.
Keywords
C-type natriuretic peptide; Internal anal sphincter; Motility; Natriuretic peptide receptor
