Ascending and descending reflex motor activity of recto-anal region—Cholinergic and nitrergic implications in a rat model

The role of PKC and RhoA/ROCK pathways in the phasic activities in the rectal smooth muscles (RSM) in the basal state is not known. We examined this issue by determining the effects of PKC inhibitors (calphostin C and Gö-6850) and a ROCK inhibitor (Y-27632) on the slow-rate (~3/min) and fast-rate (~25/min) phasic activities. We also examined the corresponding signal transduction cascades and the PKC and ROCK enzymatic activities in the RSM in the basal state. PKC inhibition with calphostin C and Gö-6850 (10(-5) M) caused a significant decrease (~25%) in slow-rate (but not fast-rate) phasic activity (monitored by frequency and amplitude of contractions) of the RSM. Conversely, ROCK inhibition with Y-27632 (10(-5) M) caused a significant decrease not only in slow-rate, but also fast-rate, phasic activity caused by ROCK inhibition in the RSM. Western blot analysis revealed that the PKC inhibition-induced decrease in RSM phasic activity was associated with decreases in PKCα translocation, phosphorylated (Thr(38)) PKC-potentiated inhibitor (CPI-17), and phosphorylated (Thr(18)/Ser(19)) 20-kDa myosin regulatory light chain. Conversely, decreases in the phasic activity in the RSM by ROCK inhibition were accompanied by the additional decrease in phosphorylated (Thr(696)) myosin phosphatase target subunit 1. Data show that while PKC and RhoA/ROCK pathways play a significant role in slow-rate high-amplitude spontaneous phasic activity, only the RhoA/ROCK pathway primarily mediates fast-rate low-amplitude phasic activity, in the RSM. Such knowledge is important in the understanding of the pathophysiology of large intestinal motility disorders. Relative contributions of the PKC vs. the RhoA/ROCK pathway in the phasic activity remain to be determined.

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“…Such phasic activity in the RSM in synchrony with colonic activity may participate in the colorectal excitatory reflex (27).…”

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confidence: 99%

Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle

Singh

Rattan

2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The time course and concentration for drug treatment was as follows: tetrodotoxin, 0.1 μmol/L, 10 min; atropine, 0.3 μmol/L, 15 min; N G -nitro-L-arginine, 0.5 mmol/L, 15 min; and L-arginine, 0.5 mmol/L, 15 min. When the drugs were added consecutively (atropine plus N G -nitro-L-arginine or atropine plus L-arginine) the time course was 30 min [12,19] .…”

Section: Protocol Designmentioning

confidence: 99%

“…Mechanographic and electrophysiological observations have demonstrated that the motor activity of the mammalian large intestine can occur in isolated preparations, thus indicating that the reflex pathways underlying intestinal motility are contained within the gut wall [2][3][4][5] . In the recto-anal region, colorectal stimulatory [6] , rectocolonic inhibitory [7,8] and colo-anal [9] , ano-rectal [10] , and rectoanal excitatory [11,12] reflex pathways have been demonstrated. It is believed that the physiological significance of recto-anal evacuatory activity is mainly attributed to the autonomic recto-anal inhibitory reflex underlying the functional nature of rectal discrimination.…”

Section: Introductionmentioning

confidence: 99%

Locality-dependent descending reflex motor activity in the anal canal–cholinergic and nitrergic contributions in the rat model

et al. 2009

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Aim: Since the distal part of the intestine is targeted by a wide range of pathogens, the motility of the recto-anal region has been the object of many experimental and clinical observations. In this study, we investigated descending motor responses in the anal canal as a measure of the activation of autonomic reflex pathways underlying evacuatory recto-anal activity. Methods: The partitioned organ bath method was used to register motor responses of the anal canal as induced by balloon distension of the rectum in isolated rat recto-anal preparations. Results: Distension-induced descending responses of the anal canal comprised contractions (with distension at a distance of 15 mm), initial contractions and secondary relaxations (at 10 mm) and short contractions followed by deep relaxations (at 3−5 mm). Decreasing the distance between the distension stimulus and the anal canal resulted in a decreased contraction response and increased relaxation. Tetrodotoxin (0.1 μmol/L) inhibited these responses. Atropine (0.3 μmol/L) decreased contraction and did not change the relaxation response. N G -nitro-L-arginine (0.5 mmol/L) enhanced contraction in both the absence and presence of atropine. L-arginine (0.5 mmol/L) inhibited contraction and extended relaxation in atropine-pretreated preparations. The actions of N G -nitro-L-arginine and L-arginine were more pronounced in the aboral direction. ChAT-positive nerve fibers were observed in myenteric ganglia of the rectum and the anal canal. The density of NADPH-diaphorase-positive neurons was higher in the anal canal region. Conclusion: Our results suggest that locality-dependent activation of the descending reflex neuromuscular communications underlie evacuatory activity in the recto-anal region. This activation response involves long excitatory cholinergic and non-cholinergic pathways along the rectum and short inhibitory nitrergic pathways located predominantly in the anal canal region.

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“…The motor activity of the anal canal was measured between two opposite sides of the ring's circumference. The anal canal was stretched under an initial tension equivalent to 10 mN [21]. Strain gauges (Microtechna, Prague, Czech Republic), stimulators and amplifiers (Experimetria, Budapest, Hungary) and recorders (TZ 4620, Laboratorni pristroje, Prague, Czech Republic) were used to record motor responses.…”

Section: Partitioned Organ Bath Methodsmentioning

confidence: 99%

“…The drugs were administered for the following times: tetrodotoxin, 10 min; NG-nitro-Larginine, 15 min; L-arginine, 15 min; atropine, 15 min. When the drugs were added consecutively (atropine plus NG-nitro-L-arginine or atropine plus L-arginine) the time course of drug action was 30 min [21].…”

Section: Protocol Designmentioning

confidence: 99%

Modular and functionally-different descending recto-anal motor pathways in a rat model

et al. 2011

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We evaluated the motor responses in recto-anal preparations obtained from rats, in terms of the excitation displayed by modules of nerve networks and descending distally directed pathways, when subjected to the mechanographic on-line technique, a partitioned organ bath, electrical stimulation (EFS, 0.8 ms, 5 Hz) and distension. EFS elicited modular contractions, which increased in amplitude distally, in circular muscle rings isolated from the proximal, middle or distal rectum. The modular responses of the internal anal sphincter or anal canal were relaxation or contraction, respectively. The application of EFS to the distal rectum induced a descending contractile response in the anal canal (5.24±0.34 mN), while distension by balloon evoked a descending response consisting of contraction (1.72±0.20 mN) followed by relaxation (3.42±0.24 mN). The responses were sensitive to tetrodotoxin. Atropine considerably depressed the contractions in all preparations. Whether or not atropine was present, L-NNA increased the excitatory responses, while L-arginine decreased the contractions and extended the relaxation of internal anal sphincter and anal canal. The results suggest that excitatory neurotransmission(s) expressed in the distal rectum dominate modular nerve networks. Functionally-different descending pathways are involved in the motor activity of the anal canal. Stimulatory cholinergic pathways are dependent on the electrically-induced excitation, and inhibitory nitrergic pathways are sensitive to distension of rectal wall.

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Ascending and descending reflex motor activity of recto-anal region—Cholinergic and nitrergic implications in a rat model

Cited by 9 publications

References 53 publications

Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle

Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle

Locality-dependent descending reflex motor activity in the anal canal–cholinergic and nitrergic contributions in the rat model

Modular and functionally-different descending recto-anal motor pathways in a rat model

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