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Biomedical subjects

M Storr

Publications and source records attributed to M Storr.

At least 37 records · Page 2Linked to original sources
PubMed2002

Endoscopic treatment of a Zenker's diverticulum using argon plasma coagulation in a patient with massive cachexia and esophageal obstruction: a case report and review of literature.

A case report is presented of an 86-year-old man in a very poor general condition with a 10-year history of a Zenker's diverticulum as a cause of a complete obstruction of the esophagus with subsequent aphagia and massive cachexia. Because of high surgical risk and contraindications to general anesthesia, an approach with the flexible endoscope to perform cricopharyngeal myotomy was undertaken. Several attempts with the flexible endoscope by experienced investigators had been performed until the esophageal inlet was intubated and argon plasma coagulation could be applied in several sessions to divide the tissue bridge between the esophagus and the Zenker diverticulum to successfully restore the pharyngoesophageal passage.

Aged↗
PubMed2002

Effect of cannabinoids on neural transmission in 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.

Animals↗
PubMed2001

Characterization of vagal input to the rat esophageal muscle.

There is recent morphological evidence for an interaction of autonomic nerve fibers and extrinsic motor nerves of the rat esophagus. The aim of the present study was to investigate a possible functional role of this autonomic innervation of vagal motor fibers on rat esophageal smooth and striated muscle function in vitro. The entire esophagus with both Nn vagi, including the Nn recurrentes, was dissected and placed in an organ bath with oxygenated Krebs-Ringer buffer. Contractile activity was measured in longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm apart from the esophagus. Vagal stimulation, applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response, which was completely blocked by tetrodotoxin (10(-6) M). The first part consisted of a tetanic striated muscle contraction, which was abolished by tubocurarin (10(-5) M) but unaffected by atropine (10(-6) M) or hexamethonium (10(-4) M). In contrast, the second part was completely abolished by hexamethonium (10(-4) M) and atropine (10(-6) M), whereas tubocurarine (10(-5) M) showed no influence, suggesting a stimulation of preganglionic nerve fibers supplying esophageal smooth muscle (muscularis mucosae). In order to characterize possible autonomic transmitters of the ENS of the esophagus, the following experiments were carried out. The magnitude of the striated muscle response was unaffected by VIP (10(-7) M), 5-HT (10(-6) M) and galanin (10(-8) - 10(-7) M), whereas they caused an inhibition of the smooth muscle response (VIP: -53.8 +/- 4.2%; galanin 10(-8) M: - 18.5 +/- 2.2%; 10(-7) M: -40.4 +/- 2.9%; 5-HT: -78.2 +/- 2.1%). The inhibitory effects of VIP and galanin on smooth muscle were reversible by the antagonists VIP 10-28 and galanin 1-15. In the presence of the nitric oxide synthase (NOS) inhibitor L-NNA (10(-4) M), the smooth and striated muscle contraction were not significantly influenced. Exogenous application of the NO-donor DEA-NO (10(-4) M) reduced the smooth muscle contraction by -81.6 +/- 7.4%, but had no significant effect on the striated muscle contraction. Though immunohistochemical findings are highly suggestive of an nitrergic autonomic modulation of striated muscle contraction by enteric neurons, we could not demonstrate a NO-mediated action on striated muscle activity. Therefore, the physiological relevance of the immunohistochemical findings remain unclear.

Animals↗
PubMed2001

[Hemosuccus pancreaticus (bleeding into the pancreatic duct). A rare complication of pancreatitis].

HISTORY AND ADMISSION FINDINGS: A 41-year-old man was admitted because of recurrent tarry stools and dizziness. Chronic pancreatitis induced by alcoholism was known. The main abnormal laboratory finding was anaemia (haemoglobin 4.6 g/dl, erythrocytes 2.28/fl). INVESTIGATIONS, TREATMENT AND COURSE: At endoscopy of the oesophagus, stomach and duodenum, fresh blood was found in the duodenum, a small trickle of blood coming from the papilla of Vater. Endoscopic retrograde cholangiography discovered no abnormality in the biliary system. Selective contrast imaging of the pancreatic duct demonstrated a short prepapillary stenosis and a prestenotic dilatation (up to 15 mm diameter) of the pancreatic duct with a cloudy contrast filling defect. After catheter withdrawal from the pancreatic duct blood spurted from the papilla. Emergency angiography revealed pseudoaneurysmatic dilatation of the gastroduodenal artery in the region of the head of the pancreas. At selective catheterization this artery was successfully occluded with metal coils placed both proximally and distally to the source of bleeding. CONCLUSION: Gastrointestinal bleeding is a rare but potentially life-threatening complication of pancreatitis. When searching for bleeding in the upper gastrointestinal tract, the papilla of Vater should be looked for as a possible source. Bleeding from the pancreas occurs particularly in pancreatitis, pancreatic pseudocyst or pancreatic tumour.

Adult↗
PubMed2001

Treatment of achalasia: botulinum toxin injection vs. pneumatic balloon dilation. A prospective study with long-term follow-Up.

BACKGROUND AND STUDY AIMS: In patients with achalasia, intrasphincteric injection of botulinum toxin (BTX) has been suggested as an alternative regimen to balloon dilation and has been shown to be superior to placebo injection. The aim of the present study was to test the effectiveness, the long-term outcome and the cumulative costs of BTX injection in consecutive patients with symptomatic achalasia in comparison with pneumatic balloon dilation. PATIENTS AND METHODS: 37 patients, who presented with symptomatic achalasia between January 1994 and December 1996 were treated with either BTX injection (n = 23) or pneumatic dilation (n = 14). Patients with short-term or long-term symptomatic failures of the initial procedure were treated again, either with the same or with the alternative method, depending on the initial response and on the patient's wish. Symptoms were assessed using a global symptom score (0 - 10) which was evaluated before treatment and 1 week, 1 month and then every 6 months after the treatment. In addition, body weight and recurrence of symptoms were noted and manometry was carried out before and after treatment. The patients were regularly contacted for the long-term follow-up. RESULTS: There were significant improvements in the global symptom scores of all patients treated, in both the BTX injection group (before 8.2 +/- 1.3, after 3.0 +/- 1.6) and the dilation group (before 8.3 +/- 1.1, after 2.3 +/- 1.9). There was also a significant decrease of lower esophageal sphincter pressure after treatment in the BTX group and the dilation group. There were no significant differences with regard to overall treatment failure and long-term outcome between patients who had or had not received previous treatment. No major complications were encountered in either group. An actuarial analysis over 48 months comparing patients receiving BTX injection or balloon dilation demonstrated that after 12 months neither therapy was significantly superior. After 24 months a single pneumatic dilation was superior to a single BTX injection, and after 48 months all patients treated by BTX injection had experienced a symptomatic relapse. In contrast, 35 % of all patients treated by dilation and 45 % of patients treated successfully by dilation were still symptom-free in an intention-to-treat analysis after 48 months. When the overall costs of treatment and further treatment after recurrence were compared, dilation and BTX injection showed a similar cost-effectiveness (costs per symptom-free day) after 48 months. CONCLUSIONS: BTX injection, which can be performed in an outpatient setting, is as safe and cost-effective as balloon dilation in symptomatic achalasia. Taking into account the lower long-term efficacy of BTX injection therapy, however, it is an alternative only in a minority of older or high-risk patients.

Actuarial Analysis↗
PubMed2001

Autoantibody profile in progressive systemic sclerosis as markers for esophageal involvement.

We investigated the relationship between the severity and extent of esophageal involvement in patients with progressive systemic sclerosis (PSS) and the autoantibody profile. We studied 37 consecutive patients with PSS and compared their results to 25 healthy volunteers. Patients with PSS were separated into three subgroups: group 1 (antinuclear antibody [ANA] [+/-], anti-Sc170 antibody [Scl70] [-], and anticentromere antibody [ACA] [-]), group 2 (ANA [+], Scl70 [+], and ACA [-]), and group 3 (ANA [+], Scl70 [-], and ACA [+]). The lower esophageal sphincter pressure and the mean proximal esophageal amplitude were significantly lower in group 3 when compared with group 1, group 2, and the healthy controls. Distal esophageal aperistalsis was noted in 85% of group 3, 40% of group 2, and 30% of group 1. An involvement of esophageal motility was found in 100% of the patients with ACA. Our results suggest that esophageal involvement is more pronounced in patients with PSS with ACA as compared with patients with only Sc170 or ANA.

Adult↗
PubMed2001

Pharmacoeconomic issues of the treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a gastroenterologist's practice. Gastroesophageal reflux (GER) describes the retrograde movement of gastric contents through the lower oesophageal sphincter (LES) to the oesophagus. GER can occur physiologically and may be accompanied by symptoms. The introduction of endoscopes and ambulatory devices for continuous monitoring of oesophageal pH (24 h pH monitoring) has led to great improvement in the ability to diagnose reflux disease and reflux-associated complications. The development of pathological reflux and GERD can be attributed to many factors. Pathophysiology of GERD includes transient lower oesophageal sphincter relaxations (TLESRs), incompetent LES because of a decreased lower oesophageal sphincter pressure (LESP) and deficient or delayed oesophageal acid clearance. Uncomplicated GERD may be treated by modification of lifestyle and eating habits in an early stage of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H2-blockers, prokinetics and proton pump inhibitors (PPIs). Although these drugs are effective, they do not necessarily influence the underlying causes of the disease by improving the oesophageal clearance, increasing the LESP or reducing the frequency of TLESRs. The following article gives an overview regarding current concepts of the pathophysiology and pharmacological treatment of GERD stressing on pharmacoeconomic issues of the treatment and discusses the advantages and disadvantages for step-up and step-down therapy.

Antacids↗
PubMed2001

Current concepts on pathophysiology, diagnosis and treatment of diffuse oesophageal spasm.

Diffuse oesophageal spasm is a functional oesophageal motility disorder of unknown aetiology, which appears to be due to a disturbance of the normal pharmacological timing of propulsive contraction occurring in the oesophageal body after swallowing. The lack of pathophysiological understanding may be due to the fact that there is more than one pathophysiological pathway causing symptoms of diffuse oesophageal spasm. Barium studies, oesophageal scintigraphy and fiberoptic examination can be helpful in finding the correct diagnosis, but manometry is still the gold standard of diagnostic procedures. Similar to other spastic oesophageal motility disorders, pharmacological treatment of diffuse oesophageal spasm includes nitrates, calcium antagonists, anticholinergics and antidepressants with varying beneficial effects. Botulinum toxin, which provides sufficient treatment as measured by symptom score and manometric patterns in patients with achalasia, was recently evaluated for the treatment of diffuse oesophageal spasm in small patient selections with promising results.

Biofeedback, Psychology↗
PubMed2001

Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up.

BACKGROUND: Diffuse esophageal spasm is a rare esophageal motility disorder for which there are no satisfactory pharmacologic alternatives for treatment. The aim of this study was to investigate whether botulinum toxin (BTX) injection is an effective short- and long-term treatment for patients with symptoms caused by diffuse esophageal spasm. Whether recurrence of clinical symptoms can be successfully retreated by BTX injection was also studied. METHODS: Nine symptomatic patients (6 women, 3 men; 57-86 years) with manometrically proven diffuse esophageal spasm underwent BTX injection. One hundred IU BTX were diluted in l0 mL of saline solution and injected endoscopically at multiple sites along the esophageal wall beginning in the region of the lower esophageal sphincter and moving proximally in 1- to 1.5-cm intervals, and into endoscopically visible contraction rings. Symptom scores based on an analogue scale for dysphagia, regurgitation, and noncardiac chest pain were assessed before and after therapy, 1 day thereafter, and at 1 and 6 months. RESULTS: Symptoms improved immediately in 7 (78%) patients after 1 injection session. After 4 weeks 8 (89%) patients were in remission with a decrease in total symptom score. The total symptom score decreased from a median 8.0 (interquartile range: 6.75; 9.0) before treatment to 2.0 (1.5; 3.75) after 1 day (p < 0.01) and to 2.0 (interquartile range: 0.75; 3.0) after 1 month (p < 0.01). After 6 months all 8 patients with a response at 1 month still had a symptom score of 3 or less without further treatment. Subsequently 4 patients required reinjection 8, 12, 15, or 24 months after the initial treatment with similarly good results. No serious adverse effects were observed. CONCLUSIONS: BTX injection at several levels of the tubular esophagus is an effective treatment for patients with symptoms caused by diffuse esophageal spasm. Symptom relapse can be effectively treated by repeated BTX injection.

Aged↗
PubMed2000

Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: pharmacokinetics, pharmacodynamics and immunomodulatory effects.

This is the first report of the serum profile of a glycosylated recombinant form of human IL-6 (rhIL-6) administered subcutaneously (1-10 microg/kg/day) in a phase I/II trial as a thrombopoietic agent in patients with advanced cancer. The pharmacodynamic effects of IL-6 were also examined. Detailed pharmacokinetic measurements were made in four patients. Peak concentrations at 5-8 h and a median t0.5 of ca. 5 h were similar to those previously reported for non-glycosylated IL-6. However, higher peak concentrations and apparent differences in effective dose levels to those previously reported with the non-glycosylated form were seen. Indications of an apparent attenuation in circulating IL-6 concentrations with continuing injections were seen in eight of 10 patients examined but anti-IL-6 antibody generation was seen in only two patients. Soluble interleukin 6 receptor concentrations generally decreased. No major changes in T cell subsets were seen but expression of CD25 and CD54 by T lymphocytes significantly increased, accompanied by marked increases in soluble CD25 (sIL-2R) and CD54 (sICAM-1). No consistent change in B cells, monocytes or NK cells were seen. No evidence for induction of TNF-alpha was found. This study demonstrates similar biological effects of glycosylated rhIL-6 to those reported for the non-glycosylated form but illustrates several apparent differences which are discussed further.

Adjuvants, Immunologic↗
PubMed2000

Endomorphin-1 and -2, endogenous ligands for the mu-opioid receptor, inhibit striated and smooth muscle contraction in the rat oesophagus.

Recently, morphological evidence for an interaction of autonomic nerve fibres and extrinsic motor innervation of the rat oesophagus has emerged. The aim of the present study was to investigate the possible influence of endogenous and exogenous opioids on rat oesophageal smooth and striated muscle function in vitro. The entire oesophagus (excluding the lower oesophageal sphincter) with both Nervi (Nn) vagi, including the Nn recurrentes, was dissected and placed in an organ bath (100 mL, 37 degrees) with oxygenated Krebs-Ringer buffer. Contractile activity was measured in a longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm distant from the oesophagus. Vagal stimulation (VS), applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response that was completely blocked by 10(-6) M tetrodotoxin. The first part consisted of a tetanic striated muscle contraction, as it was abolished by tubocurarine (10(-5) M, n=5) but unaffected by atropine (10(-6) M, n=3) or hexamethonium (10(-4) M, n=4). In contrast, the second part was completely inhibited by hexamethonium (10(-4) M) and atropine (10(-6)M), whereas tubocurarine (10(-5) M) showed no influence, indicating a stimulation of preganglionic nerve fibres supplying oesophageal smooth muscle (muscularis mucosae) via relays in myenteric ganglia. In order to characterize opioid influence on the oesophageal striated and smooth muscle contractility, the following experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous mu-opioid-receptor agonists, reduced the contractile response of the striated (EM-2, -25.1+/-5.3%; n=16), and the smooth muscle (EM-2, -81.9+/-3.3%; n=11). Both effects were reversible by the opioid receptor antagonist naloxone (10(-6) M) and therefore, mediated via opioid receptors. Neither SNC-80, an agonist on the delta-opioid-receptor, U-69593, an agonist on the kappa-opioid-receptor, nor nociceptin, an agonist at the ORL1 (opioid receptor-like) receptor, had a significant effect on the striated muscle contraction. In contrast to SNC-80, U-69593 and nociceptin inhibited smooth muscle contraction but this relaxation could not be antagonized by naloxone. None of the opioid receptor antagonists used had an effect on basal tonus or muscle contraction following VS. Our data provide evidence for an autonomic modulation of vagal motor innervation of the striated and smooth oesophageal muscle. Endomorphin-1 and -2, both selective mu-opioid receptor agonists, cause an inhibition of striated and smooth muscle response which is reversible by naloxone, an opioid receptor antagonist. The location of the mu-opioid receptor still has to be established.

Animals↗
PubMed2000

Mechanisms of alpha,beta-methylene atp-induced inhibition in rat ileal smooth muscle: involvement of intracellular Ca2+ stores in purinergic inhibition.

1. In order to investigate purinergic effects on rat ileal smooth muscle, we used alpha,beta-methylene ATP (alpha,beta-MeATP), ATP, ADP and UTP. alpha,beta-Methylene ATP and ATP were the only agonists that caused a concentration-dependent inhibition of carbachol-precontracted smooth muscle. The inhibitory effect of alpha,beta-MeATP was completely blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) mol/L), a selective antagonist of the P2X > > P2Y receptor. 2. Using reverse transcription-polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation. 3. The alpha,beta-MeATP-induced inhibition was blocked in a concentration-dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10(-7) mol/L), 4-aminopyridine (10(-4)mol/L), glibenclamide (10(-5) mol/L) and tetraethylammonium (10(-3) mol/L). 4. The alpha,beta-MeATP-induced inhibition was unaffected by pretreatment with atropine (10(-6) mol/L), phentolamine (10(-6) mol/L), propranolol (10(-6) mol/L), nitrendipine (10(-7) mol/L), pertussis toxin (10(-6) mol/L) NG-nitro-L-arginine (3 x 10(-4) mol/L) and tetrodotoxin (10(-6) mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G-protein involvement in purinergic-mediated inhibition. 5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+-ATPase inhibitor. The inhibitory effect of alpha,beta-MeATP was completely abolished after depletion of the intracellular Ca2+ stores. 6. This is in contrast with the effects seen for neurotensin, where neurotensin-induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin-sensitive non-adrenergic, non-cholinergic inhibition in rat ileal smooth muscle. 7. According to our results, the inhibitory effect of alpha,beta-MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G-protein-independent activation of an apamin-sensitive K+ channel and requires filled intracellular Ca+ stores.

Adenosine Triphosphate↗
PubMed2000

Modulatory effect of endogenous and exogenous opioids on the excitatory reflex pathway of the rat ileum.

The ascending excitatory reflex is part of the peristaltic reflex, an important participant in intestinal propulsion. The aim of this study was to characterize the role of different opioid receptors in the ascending reflex through exogenous application of non-selective (Met-enkephalin) and selective opioid agonists (mu-PLO17, delta-DPDPE, kappa-U-50, 488) as well as selective opioid receptor antagonists (mu: CTOP-NH(2), delta: ICI-174,864, kappa: Nor-Binaltorphimine). Metenkephalin (IC(50): 0.06 microM) and morphine (IC(50): 1.8 microM) inhibited the ascending reflex response concentration-dependently. Both the mu-selective agonist PLO17 (IC(50): 0.83 microM, n =11) and the kappa-selective agonist U-50,488 (IC(50): 0.68 microM, n =8) concentration-dependently inhibited the magnitude of the ascending contractile reflex response, whereas the delta-agonist DPDPE (10(-10)-10(-6)M) had no significant effect. In contrast, the latency of the response (time interval between start of the stimulus and onset of the contraction) was significantly prolonged by PLO17 > morphine > Met-enkephalin > DPDPE, whereas U-50,488 showed no effect. When the effect of the receptor-specific antagonists was tested, only CTOP-NH(2)and Nor-BNI caused a significant increase of the contractile response, whereas ICI-174 864 was ineffective. On the other hand, CTOP-NH(2)> ICI-174 864 decreased the latency significantly but the kappa-receptor agonist Nor-BNI had no influence. Thus, mu- and kappa-receptors seem to be involved in regulating the contraction strength of the ascending reflex, whereas both mu- and delta-receptors seem to be involved in the timing of the reflex response.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Pathophysiology and pharmacological treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a gastroenterologist's practice. Gastroesophageal reflux describes the retrograde movement of gastric contents through the lower esophageal sphincter (LES) to the esophagus. It is a common, normal phenomenon which may occur with or without accompanying symptoms. Symptoms associated with GERD include heartburn, acid regurgitation, noncardiac chest pain, dysphagia, globus pharyngitis, chronic cough, asthma, hoarseness, laryngitis, chronic sinusitis and dental erosions. The introduction of fiberoptic instruments and ambulatory devices for continuous monitoring of esophageal pH (24-hour pH monitoring) has led to great improvement in the ability to diagnose reflux disease and reflux-associated complications. The development of pathological reflux and GERD can be attributed to many factors. Pathophysiology of GERD includes incompetent LES because of a decreased LES pressure, transient lower esophageal sphincter relaxations (TLESRs) and deficient or delayed esophageal acid clearance. Uncomplicated GER may be treated by modification of life style and eating habits in an early stage of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2) blockers, prokinetics and proton pump inhibitors. Although these drugs are effective, they do not necessarily influence the underlying causes of the disease by improving the esophageal clearance, increasing the LESP or reducing the frequency of TLESRs. The following article gives an overview regarding current concepts of the pathophysiology and pharmacological treatment of GERD.

Antacids↗
PubMed2000

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

The aim of this study was to investigate the effects of melatonin on rat gastric fundus smooth muscle. Melatonin (10(-4) to 10(-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 +/- 0.86 x 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) to 10(-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 (l0(-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 x 10(-5) M), the nitric-oxide synthase inhibitor N-nitro-L-arginine (3 x 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.

Animals↗