Rho kinase expression and its central role in ovine gallbladder contractions elicited by a variety of excitatory stimuli

Ding

Molecular Medicine Reports

et al. 2015

Cholelithiasis is a common medical condition whose incidence rate is increasing yearly, while its pathogenesis has yet to be elucidated. The present study assessed the expression of Rho-kinase (ROCK) in gallbladder smooth muscles and its effect on the contractile function of gallbladder smooth muscles during gallstone formation. Thirty male guinea pigs were randomly divided into three groups: The control group, the gallstone model group and the fasudil interference group. The fasting volume (FV) and bile capacity of the gallbladder (FB) as well as the total cholesterol (TC) and triglyceride (TG) contents of the gallbladder bile were determined. In addition, the gallbladder was dissected to identify whether any gallstones had formed. Part of the gallbladder tissue specimens were used for immunohistochemical analysis of ROCK expression in gallbladder smooth muscles. The results showed that four guinea pigs in the model group and eight in the fasudil group displayed gallstone formation, while there was no gallstone formation in the control group. The FV and FB were significantly increased in the model and fasudil groups. Similarly, the TC and TG contents of gallbladder bile were increased in these groups. The positive expression rate of ROCK in gallbladder smooth muscles in the model and fasudil groups was significantly reduced compared with that in the control group (P<0.05). The results of the present study indicated that the reduction of ROCK expression in guinea pig gallbladder smooth muscles weakened gallbladder contraction and thereby promoted gallstone formation.

Section: Discussionmentioning

confidence: 99%

Role of ROCK expression in gallbladder smooth muscle contraction

Ding

Molecular Medicine Reports

et al. 2015

“…In this case, our results become more reasonable in terms of epileptogenesis, ictogenesis and neuronal death by the accumulation of calcium in neurons after prolonged and frequent seizures. Speculatively, inhibition of this signalling may provide a broad spectrum of antiepileptic effects because the Rho/Rho‐kinase pathway seems to be the central downstream pathway that is activated by various upstream stimuli, such as activation of excitatory neurotransmitter receptors, as in the periphery ( Büyükafşar and Levent, 2003 ; Şahan‐Fırat et al , 2005 ; Büyükafşar et al , 2006b ). However, antiepileptic effects of the Rho‐kinase inhibitors should be examined in different genetically epilepsy‐prone animals, because those may be suitable models for the best evaluation of the characteristics of the effects of Rho‐kinase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic effects of two Rho‐kinase inhibitors, Y‐27632 and fasudil, in mice

İnan

Büyükafşar

2008

British J Pharmacology

Background and purpose: Rho/Rho-kinase signalling is involved in many cellular events, including some in the CNS. However, the role of this pathway in epilepsy has not yet been assessed. Therefore, we determined the effects of two Rho-kinase inhibitors, Y-27632 and fasudil, on seizures induced by pentylenetetrazole (PTZ) or maximal electroconvulsive shock (MES). Experimental approach: Effects of Y-27632 (5-10 mg kg À1 ) and fasudil (5-25 mg kg À1 ) on duration of myoclonic jerks, clonic and tonic convulsions, tonic hindlimb extensions and percentage of tonic convulsion index, as well as recovery latency for righting reflex were investigated in mice stimulated with PTZ (65 mg kg À1 ) or MES (50 Hz, 50 mA and 0.4 s). These inhibitors were also tested on a model of kindling induced by PTZ (35 mg kg À1 , for 11 days). Membrane and cytosolic levels of RhoA protein were measured in brain homogenates from kindled mice. Key results: Y-27632 and fasudil diminished onset of myoclonic jerks, clonic convulsions and tonic hindlimb extensions in mice given PTZ. These inhibitors suppressed the percentage of tonic convulsion index and recovery latency for righting reflex in the mice excited with MES. Western blotting demonstrated that Rho translocation to plasma membrane increased in the brain homogenates obtained from PTZ-kindled mice. However, the Rho-kinase inhibitors at the given doses did not change motor coordination of the mice. Conclusions and implications: Rho/Rho-kinase signalling may play a role in epilepsy induced by PTZ and MES. Furthermore, Rho-kinase inhibitors could be novel important antiepileptic agents.

“…Rho kinase-mediated deactivation of myosin light-chain phosphatase increases contractile sensitivity to cytoplasmic calcium influx whether the calcium arises from extracellular or intracellular sources. Depolarization induced by electric field stimulation (24) or pharmacologically (i.e., potassium chloride; ref. 25) have both demonstrated increases in Rho kinase activity and increases in muscle force generation.…”

Section: Discussionmentioning

confidence: 99%

Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle

Yim¹,

Gallos²,

Xu³

et al. 2011

FASEB j.

Airway smooth muscle (ASM) contraction is an important component of the pathophysiology of asthma. Taurine, an agonist of glycine receptor chloride (GlyR Cl(-)) channels, was found to relax contracted ASM, which led us to question whether functional GlyR Cl(-) channels are expressed in ASM. Messenger RNA for β (GLRB), α1 (GLRA1), α2 (GLRA2), and α4 (GLRA4) subunits were found in human (Homo sapiens) and guinea pig (Cavia porcellus) tracheal smooth muscle. Immunoblotting confirmed the protein expression of GLRA1 and GLRB subunits in ASM. Electrical activity of cultured human ASM cells was assessed using a fluorescent potentiometric dye and electrophysiological recordings. Glycine increased current and significantly increased fluorescence in a dose-dependent manner. The GlyR Cl(-) channel antagonist strychnine significantly blocked the effects of glycine on potentiometric fluorescence in ASM cells. Guinea pig airway ring relaxation of ACh-induced contractions by isoproterenol was significantly left-shifted in the presence of glycine. This effect of glycine was blocked by pretreatment with the GlyR Cl(-) channel antagonist strychnine. Glycine treatment during tachykinin- and acetylcholine-induced contractions significantly decreased the maintenance of muscle force compared to control. GlyR Cl(-) channels are expressed on ASM and regulate smooth muscle force and offer a novel target for therapeutic relaxation of ASM.