Evidence for the presence and release of BDNF in the neuronal and non‐neuronal structures of the internal anal sphincter

2021 ◽  
Author(s):  
Arjun Singh ◽  
Jagmohan Singh ◽  
Satish Rattan
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter

scholarly journals Rhythmic calcium transients in smooth muscle cells of the mouse internal anal sphincter

2019 ◽  
Vol 32 (3) ◽  
Author(s):  
Caroline A. Cobine ◽  
Karen I. Hannigan ◽  
Megan McMahon ◽  
Emer P. Ni Bhraonain ◽  
Salah A. Baker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Muscle Cells ◽  
Calcium Transients

scholarly journals Topohistology of the Paravaginal Nerves and Fasciae with Special Reference to Nerves to the Internal Anal Sphincter

2014 ◽  
Vol 67 (8) ◽  
pp. 495-503
Author(s):  
Fumitake Hata ◽  
Takashi Arakawa ◽  
Kuniaki Okada ◽  
Hidefumi Nishimori ◽  
Shinichiro Ikeda ◽  
...  
Keyword(s):  
Special Reference ◽  
Anal Sphincter ◽  
Internal Anal Sphincter

scholarly journals RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

2012 ◽  
Vol 302 (7) ◽  
pp. G664-G675 ◽  
Author(s):  
Satish Rattan ◽  
Jagmohan Singh
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Control Mechanisms ◽  
Rock Inhibitor ◽  
Critical Determinant ◽  
Molecular Control ◽  
Motility Disorders ◽  
Basal Tone ◽  
Before And After ◽  
Rational Therapy

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8to 10−4M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

EUS-Guided Botulinum Toxin Injection of the Internal Anal Sphincter in Anorectal Outlet Obstruction

2014 ◽  
Vol 109 (8) ◽  
pp. 1293-1294 ◽  
Author(s):  
Arvind J Trindade ◽  
Robert Hirten ◽  
Ronald E Greenberg ◽  
Divyesh V Sejpal
Keyword(s):  
Botulinum Toxin ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Botulinum Toxin Injection ◽  
Outlet Obstruction

scholarly journals Ultrastructural changes in internal anal sphincter in neurogenic faecal incontinence.

Gut ◽  
1988 ◽  
Vol 29 (12) ◽  
pp. 1692-1698 ◽  
Author(s):  
M Swash ◽  
A Gray ◽  
D Z Lubowski ◽  
R J Nicholls
Keyword(s):  
Anal Sphincter ◽  
Faecal Incontinence ◽  
Internal Anal Sphincter ◽  
Ultrastructural Changes

scholarly journals Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a

2016 ◽  
Vol 311 (5) ◽  
pp. G964-G973 ◽  
Author(s):  
Jagmohan Singh ◽  
Ettickan Boopathi ◽  
Sankar Addya ◽  
Benjamin Phillips ◽  
Isidore Rigoutsos ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Smooth Muscles ◽  
Smooth Muscle Contractility ◽  
Network Analyses ◽  
Rhoa Signaling

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets ( Eln, Col3a1, Col1a1, Zeb2, Myocd, Srf, Smad1, Smad2, Rhoa/Rock2, Fn1, Tagln v2, Klf4, and Acta2) involved in regulation of smooth muscle contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF, and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist [U-46619 (thromboxane A2analog)]-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Last, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone and suggests that miR-133a is a feasible therapeutic target in aging-associated rectoanal incontinence.

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