The sphingosine analog fingolimod ( FTY 720) enhances tone and contractility of rat gastric fundus smooth muscle

2018 ◽  
Vol 30 (10) ◽  
Author(s):  
M. Kraft ◽  
U. K. Zettl ◽  
T. Noack ◽  
R. Patejdl
Keyword(s):  
Smooth Muscle ◽  
Gastric Fundus ◽  
Fty 720 ◽  
Rat Gastric Fundus

Relaxant effect of atorvastatin on isolated rat gastric fundus strips: implications for Ca2+-signalling mechanisms

2019 ◽  
Vol 97 (5) ◽  
pp. 413-421 ◽  
Author(s):  
Deniz Kaleli-Durman ◽  
F. İlkay Alp-Yıldırım ◽  
Osman Özdemir ◽  
B. Sönmez Uydeş-Doğan
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Mevalonate Pathway ◽  
Muscle Tone ◽  
Gastric Fundus ◽  
Lipid Lowering ◽  
Nitric Oxide Synthase Inhibitor ◽  
Relaxant Effect ◽  
Rat Gastric Fundus ◽  
Isolated Rat

Statins are determined to have various pleiotropic effects apart from their lipid-lowering properties. Herein, we investigated the direct effects of atorvastatin on gastric smooth muscle tone. Atorvastatin effectively relaxed isolated rat gastric fundus strips precontracted with acetylcholine, potassium chloride, and serotonin. Incubation of the strips with nitric oxide synthase inhibitor, l-NOARG (10−4 M, 20 min), l-type voltage-operated Ca2+ channel (VOCC) blocker, nifedipine (10−6 M, 30 min), KATP channel blocker, glibenclamide (10−5 M, 30 min), or precursor of cholesterol, mevalonate (10−2 M, 45 min) did not change the relaxations to atorvastatin. However, pretreatment of fundus strips with atorvastatin (3×10−5–3×10−4 M, 30 min) inhibited the contractions to calcium chloride (10−4–10−1 M), acetylcholine (10–4 M), and caffeine (20 mM) in the calcium-free medium. Moreover, atorvastatin reduced the contractions induced by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, cyclopiazonic acid (10−7–3×10−5 M). The current study demonstrated that atorvastatin produces an acute relaxant effect on gastric fundus strips, which appears to be mediated by several Ca2+-signalling mechanisms such as the blockade of l-type VOCC-independent Ca2+ entry, decrease in smooth muscle Ca2+ sensitivity, inhibition of IP3- and ryanodine-sensitive intracellular stores to mediate Ca2+ release, as well as the activation of SERCA. This acute relaxing effect seems unlikely to be related with nitric oxide, KATP channels, and the mevalonate pathway.

Inhibition of small conductance K+-channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus

2000 ◽  
Vol 78 (10) ◽  
pp. 799-806 ◽  
Author(s):  
M Storr ◽  
V Schusdziarra ◽  
H -D Allescher
Keyword(s):  
Smooth Muscle ◽  
Potassium Channel ◽  
Guanylate Cyclase ◽  
Inhibitory Effect ◽  
Gastric Fundus ◽  
Channel Blockers ◽  
Basal Tone ◽  
Potassium Channel Blockers ◽  
Rat Gastric Fundus ◽  
Small Conductance

The aim of this study was to investigate the effects of melatonin on rat gastric fundus smooth muscle. Melatonin (10-4 to10-3 M) had no effect on the basal tone of gastric smooth muscle. After precontraction with carbachol (10-6 M) or serotonin (10-7 M), melatonin caused a concentration dependent inhibitory action. The half maximal effect on serotonin-induced contraction was found with 1.12 beta 0.86 beta 10-5 M of melatonin. Increasing concentrations of melatonin (10-5 to 10-3 M) resulted in a right shift of the serotonin concentration response curve (10-10 to10-5 M). This inhibitory effect of melatonin was partially blocked in the presence of apamin (10-10 to 10-7 M), a specific blocker of the small conductance calcium-dependent potassium channel, but not in the presence of other potassium channel blockers like charybdotoxin (10-8 M), glibenclamide (10-5 M), or tetraethylammonium (ODQ, 10-4 M). The inhibitory effect was not changed in the presence of the neuronal blocker tetrodotoxin (10-6 M), the selective P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 × 10-5 M), the nitric-oxide synthase inhibitor N-nitro-L-arginine (3 × 10-4 M), or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (10-4 M), suggesting that neither the purinergic, nitrergic, nor guanylate cyclase pathways were involved. We further investigated inhibitory responses to electrical field stimulation (EFS) at different frequencies under non-adrenergic, non-cholinergic (NANC) conditions on a serotonin-induced contraction in the presence of melatonin (10-5 to 10-4 M). Melatonin significantly reduced these inhibitory NANC responses in higher (8-32 Hz), but not lower (05-4 Hz), frequencies (16 Hz without melatonin, 103 ± 6.3%; melatonin 10-5 M, 80.4 ± 7.5%; melatonin 10-4 M, 39.1 ± 17.1%). Melatonin had no effect on contractile responses induced by EFS under basal tone. These results demonstrate that the inhibitory effect of melatonin in rat gastric fundus smooth muscle is apamin sensitive, but is not affected by other potassium channel blockers. This suggests that melatonin may be another transmitter candidate for the apamin sensitive responses within the gastrointestinal tract.Key words: melatonin, smooth muscle, apamin, NANC-inhibition, gastric, potassium channels.

Effect of cannabinoids on neural transmission in rat gastric fundus

2002 ◽  
Vol 80 (1) ◽  
pp. 67-76 ◽  
Author(s):  
M Storr ◽  
E Gaffal ◽  
D Saur ◽  
V Schusdziarra ◽  
H D Allescher
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Physiological Role ◽  
Gastric Fundus ◽  
Dependent Manner ◽  
Receptor Agonists ◽  
Relaxant Response ◽  
Rat Gastric Fundus

The purpose of this study was to examine the possible role of cannabinoids on the neuromuscular function of rat gastric fundus. In addition to possible direct effects on smooth muscle, the influence of cannabinoids on contractile (cholinergic) and relaxant (non-adrenergic, non-cholinergic (NANC)) neural innervation of the rat gastric fundus was investigated in vitro. Neither anandamide (an endogenous cannabinoid receptor agonist) nor Win 55,212-2 and methanandamide (synthetic cannabinoid receptor agonists) nor AM 630 (a cannabinoid receptor antagonist) showed any effect on smooth muscle activity at baseline or after precontraction with 5-hydroxytryptamine (5-HT; 10–7 M). Electrical field stimulation (EFS) of the smooth muscle preparation (40 V; 5 Hz) caused cholinergically mediated twitch contractions that were abolished by atropine (10–6 M) or tetrodotoxin (TTX; 10–6 M). Anandamide and Win 55,212-2 reduced these twitch contractions in a concentration-dependent manner, an effect that could be reversed by the cannabinoid receptor antagonist AM 630 for anandamide, but not for Win 55,212-2. When NANC relaxant neural responses (presence of atropine (10–6 M) and guanethidine (10–6 M)) were induced by EFS, the cannabinoid receptor agonists anandamide and Win 55,212-2 reduced the relaxant response, an effect that could be reversed by the cannabinoid receptor antagonist AM 630 for anandamide, but not for Win 55,212-2. When given alone AM 630 caused an increase in the EFS-induced relaxant response. The presence of CB1 and CB2 cannabinoid receptor mRNA within the rat stomach was demonstrated by reverse transcription polymerase chain reaction (RT-PCR). The results of this study indicate that cannabinoids modulate excitatory cholinergic and inhibitory NANC neurotransmission in the rat gastric fundus. Endogenous cannabinoids may play a physiological role only in NANC inhibitory transmission, as AM 630 did not modify the electrically induced cholinergic contraction. The involved cannabinoid receptors are most likely located on neuronal structures. The present study also provides evidence that more than one receptor type is involved.Key words: cannabinoid, anandamide, rat gastric fundus relaxation, NANC, AM 630.

scholarly journals Effect of Cu2+ on relaxations to the nitrergic neurotransmitter, NO and S-nitrosothiols in the rat gastric fundus

1996 ◽  
Vol 119 (5) ◽  
pp. 990-996 ◽  
Author(s):  
Joris G. Man ◽  
Benedicte Y. Winter ◽  
Guy E. Boeckxstaens ◽  
Arnold G. Herman ◽  
Paul A. Pelckmans
Keyword(s):  
Gastric Fundus ◽  
Rat Gastric Fundus

Endomorphins 1 and 2 reduce relaxant non-adrenergic, non-cholinergic neurotransmission in rat gastric fundus

Life Sciences ◽  
2002 ◽  
Vol 71 (4) ◽  
pp. 383-389 ◽  
Author(s):  
M. Storr ◽  
E. Gaffal ◽  
V. Schusdziarra ◽  
H.-D. Allescher
Keyword(s):  
Gastric Fundus ◽  
Cholinergic Neurotransmission ◽  
Rat Gastric Fundus

scholarly journals Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal

2000 ◽  
Vol 279 (2) ◽  
pp. C529-C539 ◽  
Author(s):  
Anne Epperson ◽  
William J. Hatton ◽  
Brid Callaghan ◽  
Philip Doherty ◽  
Rebecca L. Walker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Expression Profiles ◽  
Interstitial Cells ◽  
Gastric Fundus ◽  
Soluble Form ◽  
Pacemaker Activity ◽  
Murine Small Intestine ◽  
Cells Of Cajal

Located within the tunica muscularis of the gastrointestinal (GI) tract are networks of cells known as interstitial cells of Cajal (ICC). ICC are critical for important basic functions of GI motility such as generation and propagation of slow-wave pacemaker activity and reception of regulatory inputs from the enteric nervous system. We have developed a novel procedure to identify and isolate individual ICC from freshly dispersed cell preparations of the murine small intestine and gastric fundus and to determine differential transcriptional expression We have compared the expression profiles of pacemaker ICC isolated from the murine small intestine (IC-MY) and ICC involved in neurotransmission from the gastric fundus (IC-IM). We have also compared expression profiles between ICC and smooth muscle cells (SMC) and between freshly isolated ICC and cultured ICC. Cultured ICC express smooth muscle myosin, whereas freshly dispersed ICC do not. All cell types express muscarinic receptor types M2and M3, neurokinin receptors NK1and NK3, and inhibitory receptor VIP-1, whereas only cultured ICC and SMC express VIP-2. Both cultured and freshly dispersed IC-IM and IC-MY express the soluble form of stem cell factor, whereas SMC from the gastric fundus express only the membrane-bound form.

Effects of acid inhibition on somatostatin-producing cells in the rat gastric fundus

2001 ◽  
Vol 103 (4) ◽  
pp. 413-422 ◽  
Author(s):  
Sema Bolkent ◽  
Selma Yilmazer ◽  
Fatma Kaya ◽  
Melek Öztürk
Keyword(s):  
Gastric Fundus ◽  
Acid Inhibition ◽  
Rat Gastric Fundus
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