In vivo and in vitro study of the influence of the anticholinesterase drug galantamine on motor and evacuative functions of rat gastrointestinal tract

Turiiski, Valentin I.; Krustev, A.; Sirakov, Vladimir N.; Getova, D.

doi:10.1016/j.ejphar.2004.07.054

Cited by 29 publications

(21 citation statements)

References 16 publications

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“…The overall effect of cholinergic stimulation of the intestinal smooth musculature appears to be excitatory, resulting in prolonged slow waves when measured in smooth muscle cells (Huizinga et al, 1984;Sanders and Smith, 1986;Seerden et al, 2005). Consistently, in barium follow-through studies in rats, those receiving galantamine (a compound that inhibits acetylcholinesterase) had decreased intestinal barium transit time and increased smooth muscle contractility (Turiiski et al, 2004). Further studies on muscarinic regulation of other ion channels in ICC and smooth muscle cells are needed to resolve the complex actions of cholinergic receptor stimulation.…”

Section: Muscarinic Regulation Of Erg Kmentioning

confidence: 62%

Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal

McKay

Huizinga

2006

J Pharmacol Exp Ther

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The interstitial cells of Cajal (ICC) of the myenteric plexus generate a set of currents that evoke a pacemaker potential that sets the initial conditions for the contraction frequency and duration of the electrically coupled intestinal musculature. The synapse-like contacts between ICC and myenteric motor nerves highlight the potential role of the enteric nervous system in regulating the pacemaking currents in ICC. The objective of the present study was to investigate muscarinic regulation of the ether-a-go-go-related gene (ERG) K ϩ current. Immunoreactivity of the M 3 receptor (M 3 R) but not the M 2 receptor was detected on murine jejunal ICC-Auerbach's plexus (ICC-AP). The muscarinic agonist bethanechol reduced hyperpolarization-evoked peak ERG currents at Ϫ100 mV by 23 Ϯ 1% and increased both fast and slow time constants of deactivation, resulting in increased steady-state currents between Ϫ55 and Ϫ35 mV. Bethanechol also increased depolarization-evoked steady-state currents by 59 Ϯ 10% at Ϫ40 mV, whereas currents were decreased at potentials positive to 0 mV. The halfmaximal voltage of activation was shifted 11.9 mV leftward. Interestingly, the time constant of activation increased only at Ϫ40 mV. Atropine prevented and 2 M E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl-4-(methylsulfonylaminobenzoyl)piperidine] inhibited bethanechol-affected currents. The effect of bethanechol was mimicked by protein kinase C (PKC) activation and diminished by PKC inhibition. Our results indicate that the ERG K ϩ channel in ICC is affected by stimulation of muscarinic receptors, probably the M 3 R, via a PKC-dependent mechanism. Modulation of the ERG K ϩ current in ICC-AP will affect the kinetics of pacemaking in the intestinal musculature.In the gastrointestinal tract, interstitial cells of Cajal associated with the myenteric plexus (ICC-AP or ICC-MP) generate a pacemaking current that is transmitted to coupled smooth muscle cells, producing an electrical slow wave that governs smooth muscle contraction (Der-Silaphet et al., 1998;Koh et al., 1998;Thomsen et al., 1998). Along the length of the intestine, there are multiple intrinsic pacemaking sites that create a stepwise gradient in frequency and, hence, transmit pacemaker-evoked slow waves toward the distal intestine, prompting anal propagation of the slow wave (Diamant and Bortoff, 1969). Without muscle excitation, slow waves do not normally bear action potentials, and little contractile activity is associated with them (Lammers and Slack, 2001). During muscle excitation, neural or otherwise, action potentials are generated by depolarized smooth muscle cells. In the circular and longitudinal muscle layers of the small intestine, the membrane potential is only sufficiently depolarized during the slow-wave plateau phase (Lammers and Slack, 2001). Because of the propagating nature of the slow waves, a peristaltic motor pattern occurs. A critically important component of peristaltic motor activity during digestion is that high-frequency pacemaker activity switches from the ...

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Section: Muscarinic Regulation Of Erg Kmentioning

confidence: 62%

Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal

McKay

Huizinga

2006

J Pharmacol Exp Ther

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“…CHI could increase gastrointestinal motility. 25,26) Our data showed that this occurred in the early period after administration. However anticholinergic medication can result in reverse effects and may have the risk of cognitive impairment due to receptor specificity and to the ability of these medications to cross the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 73%

Propantheline Attenuates the Peripheral Side Effects of Donepezil without Affecting Its Antiamnestic Properties in Cerebral Ischemic Mice

Zhu

Zhang

et al. 2008

JOURNAL OF HEALTH SCIENCE

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Cholinergic deficits are found in both vascular dementia and Alzheimer's disease (AD). Cholinesterase inhibition (CHI) is the only strategy that has been proven to have beneficial effects in patients, but may cause a broad spectrum of adverse events such as nausea, vomiting, and diarrhea, etc. To investigate how to attenuate the peripheral side effects of CHI agents without affecting their efficacy, the effects of propantheline bromide (PB) co-administered with donepezil on the gastric emptying (GE), gastrointestinal transit (GIT), brain cholinesterase (ChE) activities, and maze tasks of mice with memory impairment induced by transient ischemia were observed. The results indicated that PB decreased the increase in GE and GIT, but did not change brain acetylcholinesterase (AChE) activity or the latency of escape in cerebral ischemic mice treated with donepezil. These findings suggest that PB is nearly unable to penetrate the blood-brain barrier and could attenuate the peripheral side effects of CHI agents in the peripheral nervous system and without affecting their therapeutic effects in the central nervous system.

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“…There are certain differences in the cholinergic control throughout the gastrointestinal tract [22,23]. This presupposes involvement of a different number of receptors in each type of SM preparation, as well as an acetylcholine-induced reaction differing in strength.…”

Section: Discussionmentioning

confidence: 99%

Comparing hyoscine and drotaverine effects on colon in CT colonography

Sirakov

Getova

et al. 2011

Open Medicine

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AbstractHyoscine and drotaverine effectiveness was compared for the purposes of achieving optimum distension following insufflation in CT colonography. The in vitro effects of hyoscine and drotaverine on tone and contractility of SM preparations isolated from different areas of human colon were studied by isometric registration of contractile activity. Both medications have a relaxing effect on SM preparations and inhibit their spontaneous contractions. The drotaverine-induced effects were reliably more marked than the hyoscine-induced ones. CT colonography was performed in 70 patients who were injected with equal doses of either hyoscine (n=32) or drotaverine (n=38). The degree of drug-induced distension in both groups was determined by measuring the lumen of the colon on a 2D reconstruction. In most colon areas the width of the distended lumen was greater in the drotaverine-treated patients. We concluded that drotaverine can be used as a means to facilitate colonic distension.

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In vivo and in vitro study of the influence of the anticholinesterase drug galantamine on motor and evacuative functions of rat gastrointestinal tract

Cited by 29 publications

References 16 publications

Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal

Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal

Propantheline Attenuates the Peripheral Side Effects of Donepezil without Affecting Its Antiamnestic Properties in Cerebral Ischemic Mice

Comparing hyoscine and drotaverine effects on colon in CT colonography

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In vivo and in vitro study of the influence of the anticholinesterase drug galantamine on motor and evacuative functions of rat gastrointestinal tract

Cited by 29 publications

References 16 publications

Muscarinic Regulation of Ether-a-go-go-Related Gene K+ Currents in Interstitial Cells of Cajal

Muscarinic Regulation of Ether-a-go-go-Related Gene K+ Currents in Interstitial Cells of Cajal

Propantheline Attenuates the Peripheral Side Effects of Donepezil without Affecting Its Antiamnestic Properties in Cerebral Ischemic Mice

Comparing hyoscine and drotaverine effects on colon in CT colonography

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Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal

Muscarinic Regulation of Ether-a-go-go-Related Gene K⁺ Currents in Interstitial Cells of Cajal