Different proctolin neurons elicit distinct motor patterns from a multifunctional neuronal network.
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Distinct motor patterns are selected from a multifunctional neuronal network by activation of different modulatory projection neurons. Subsets of these projection neurons can contain the same neuromodulator(s), yet little is known about the relative influence of such neurons on network activity. We have addressed this issue in the stomatogastric nervous system of the crab Cancer borealis. Within this system, there is a neuronal network in the stomatogastric ganglion (STG) that produces many versions of the pyloric and gastric mill rhythms. These different rhythms result from activation of different projection neurons that innervate the STG from neighboring ganglia and modulate STG network activity. Three pairs of these projection neurons contain the neuropeptide proctolin. These include the previously identified modulatory proctolin neuron and modulatory commissural neuron 1 (MCN1) and the newly identified modulatory commissural neuron 7 (MCN7). We document here that each of these neurons contains a unique complement of cotransmitters and that each of these neurons elicits a distinct version of the pyloric motor pattern. Moreover, only one of them (MCN1) also elicits a gastric mill rhythm. The MCN7-elicited pyloric rhythm includes a pivotal switch by one STG network neuron from playing a minor to a major role in motor pattern generation. Therefore, modulatory neurons that share a peptide transmitter can elicit distinct motor patterns from a common target network. (+info)
Sonographic evaluation of antepartum development of fetal gastric motility.
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OBJECTIVE: Little is known about the development of fetal gastric motility and emptying. The aim of this study was to evaluate the development of gastric motility sonographically in the human fetus. METHODS: The motility and peristalsis of the fetal stomach were sonographically studied in 76 normal fetuses at 12-39 weeks of gestation. Fetal gastric motility was assessed by videotaping real-time ultrasonic images of the stomach for periods of 60 or more minutes. RESULTS: Gastric peristalsis appeared as early as 14 weeks of gestation, and was detected in all fetuses by 23 weeks. The frequency of peristaltic waves was constant, and was 2.2-3 times per minute at 14-39 weeks of gestation. The onset of fetal gastric peristalsis was sporadic and the period with no peristaltic waves was dominant before 24 weeks of gestation. Fetal gastric peristalsis increased and consolidated into long-term clusters from 24 weeks of gestation. The mean duration of peristalsis increased from 4.1 +/- 1.2 min (n = 6) at 20-23 weeks to 14.1 +/- 3.2 min (n = 14) at 32-35 weeks of gestation, and remained constant thereafter. CONCLUSIONS: Fetal gastric motility was quantified and its development during pregnancy was assessed in this study. There was a critical point of development at around 24-25 weeks of gestation when grouped peristalsis was observed in all fetuses. (+info)
Receptor for motilin identified in the human gastrointestinal system.
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Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species. It affects gastric motility by stimulating interdigestive antrum and duodenal contractions. A heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptor for motilin was isolated from human stomach, and its amino acid sequence was found to be 52 percent identical to the human receptor for growth hormone secretagogues. The macrolide antibiotic erythromycin also interacted with the cloned motilin receptor, providing a molecular basis for its effects on the human GI tract. The motilin receptor is expressed in enteric neurons of the human duodenum and colon. Development of motilin receptor agonists and antagonists may be useful in the treatment of multiple disorders of GI motility. (+info)
Detection of 1,N2-propanodeoxyguanosine adducts of 2-hexenal in organs of Fischer 344 rats by a 32P-post-labeling technique.
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2-Hexenal is an alpha,beta-unsaturated carbonyl compound which is mutagenic, genotoxic and forms cyclic 1,N2-propanodeoxyguanosine adducts like similar propenals for which carcinogenicity was shown, e.g. acrolein or crotonaldehyde. Since humans have a permanent intake of 2-hexenal via vegetarian food this genotoxic compound is considered to play a role in human carcinogenicity. The data base is, however, presently not sufficient for a cancer risk assessment. To date no long term carcinogenicity study on 2-hexenal has been published. Detection of respective DNA adducts of this substance in animals or humans could allow cancer risk assessment. Therefore, we have developed a 32P-post-labeling technique based on nuclease P1 enrichment and TLC separation of the labeled adducts. The respective adducts are stable over a wide pH range from pH 4 to pH 11 and relatively stable against nuclease P1. The detection limit was 0.03 adducts per 10(6) nucleotides and the recovery was 10%. With this method we have shown in vivo formation of 1,N 2-propanodeoxyguanosine adducts of 2-hexenal for the first time and found the respective DNA adducts in different organs of Fischer 344 rats after gavage of 500, 200 and 50 mg 2-hexenal/kg body wt. No adducts could be detected in the organs of untreated rats. There is a clear dependence of the adduct level and the CBI (covalent binding index) on the dose. The CBI of 2-hexenal calculated on the basis of our adduct levels is extremely low (0.06). Since intake of 2-hexenal via fruit and vegetables is very low the cancer risk from 2-hexenal intake via food must also be considered as very low according to a first raw estimation on the basis of CBI and intake. The situation deserves, however, a more precise risk assessment in the future. (+info)
Pharmacological analysis of CCK2 receptor antagonists using isolated rat stomach ECL cells.
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1. Gastrin stimulates rat stomach ECL cells to secrete histamine and pacreastatin, a chromogranin A (CGA)-derived peptide. The present report describes the effect of nine cholecystokinin2 (CCK2) receptor antagonists and one CCK1 receptor antagonist on the gastrin-evoked secretion of pancreastatin from isolated ECL cells. 2. The CCK2 receptor antagonists comprised three benzodiazepine derivatives L-740,093, YM022 and YF476, one ureidoacetamide compound RP73870, one benzimidazole compound JB 93182, one ureidoindoline compound AG041R and three tryptophan dipeptoids PD 134308 (CI988), PD135158 and PD 136450. The CCK1 receptor antagonist was devazepide. 3. A preparation of well-functioning ECL cells (approximately 80% purity) was prepared from rat oxyntic mucosa using counter-flow elutriation. The cells were cultured for 48 h in the presence of 0.1 nM gastrin; they were then washed and incubated with antagonist alone or with various concentrations of antagonist plus 10 nM gastrin (a maximally effective concentration) for 30 min. Gastrin dose-response curves were constructed in the absence or presence of increasing concentrations of antagonist. The amount of pancreastatin secreted was determined by radioimmunoassay. 4. The gastrin-evoked secretion of pancreastatin was inhibited in a dose-dependent manner. YM022, AG041R and YF476 had IC50 values of 0.5, 2.2 and 2.7 nM respectively. L-740,093, JB93182 and RP73870 had IC50 values of 7.8, 9.3 and 9.8 nM, while PD135158, PD136450 and PD134308 had IC50 values of 76, 135 and 145 nM. The CCK1 receptor antagonist devazepide was a poor CCK2 receptor antagonist with an IC50 of about 800 nM. 5. YM022, YF476 and AG041R were chosen for further analysis. YM022 and YF476 shifted the gastrin dose-response curve to the right in a manner suggesting competitive antagonism, while the effects of AG041R could not be explained by simple competitive antagonism. pK(B) values were 11.3 for YM022, 10.8 for YF476 and the apparent pK(B) for AG041R was 10.4. (+info)
Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization.
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Retinoids exhibit multiple functions through interaction with nuclear retinoid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastric carcinogenesis, we have used in situ hybridization to investigate expression of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric cancer tissues were hybridized with non-radioactive RNA probes for subtypes of RAR and RXR. Expression of RAR alpha, RAR beta, RAR gamma, RXR alpha and RXR beta was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expression of RAR alpha and RAR beta were found in three and seven cancer tissues, respectively, and levels of RXR alpha mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nuclear retinoid receptors, only expression of RAR alpha mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compared to adjacent normal tissues. In conclusion, normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retinoic acid on normal gastric mucosa. The decrease in RAR alpha expression in premalignant and malignant gastric tissues suggests a significant role of RAR alpha during gastric carcinogenesis. (+info)
High intake of milk fat inhibits intestinal colonization of Listeria but not of Salmonella in rats.
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During fat digestion, fatty acids and monoglycerides are liberated in the gastrointestinal tract. Generally, these lipids are potent inhibitors of gram-positive bacteria in vitro but have less effect on gram-negative microbes. Considering this, we hypothesized that increased intake of bovine milk fat would result in enhanced gastrointestinal killing of Listeria monocytogenes (gram-positive) but have little effect on infection with Salmonella enteritidis (gram-negative) in rats. To test this, rats were fed either low milk fat diets (10% of energy obtained from milk fat, corresponding to 4. 2 g fat/100 g diet) or high milk fat diets (40% of energy obtained from milk fat, corresponding to 19.6 g fat/100 g diet). After adaptation to these diets, rats were orally infected with Listeria or Salmonella. Greater milk fat consumption in Listeria-infected rats diminished intestinal colonization of Listeria (P < 0.05) and reduced diarrhea (P < 0.05). Analysis of gastrointestinal contents showed that killing of Listeria occurred predominantly in the stomach. High milk fat intake significantly augmented this gastric listericidal capacity (P < 0.05) and raised the concentration of medium-chain and saturated long-chain free fatty acids and of monoglycerides of C12:0, C14:0, C16:0, C18:0, and C18:1 in gastric chyme (P < 0.05). Considering the in vitro listericidal capacity of these agents, it was concluded that particularly the free fatty acids C10:0, C12:0 and C14:0 and the monoglycerides of C12:0, C14:0, and C16:0 seem to play a pivotal role in this enhanced Listeria killing. In contrast, Salmonella infection was not affected by milk fat consumption. In conclusion, high milk fat intake results in higher concentrations of gastric bactericidal lipids and thereby protects against Listeria infection but not against Salmonella. (+info)
Expression of constitutive nitric oxide synthase in rat and human gastrointestinal tract.
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The aim of this study was to determine the expression of constitutive NO synthases (ecNOS and bNOS) at the protein level in rat and human gastrointestinal tract. We established a quantitative Western blotting method for detection and quantification of ecNOS and bNOS in both species. Human gastric fundus was further analyzed by immunohistochemistry. EcNOS expression at the protein level could be quantified in different organs of the rat gastrointestinal tract and in human gastric mucosal biopsies. Immunohistochemistry of gastric fundus revealed that immunoreactivity for ecNOS was localized mainly in the endothelium of small vessels. In rats, expression of bNOS at the protein level was highest in esophagus. By means of immunohistochemistry of human gastric fundus, immunoreactivity was detected mainly in the plexus of Auerbach. We conclude that isoforms of constitutive nitric oxide synthase can be identified and quantified at the protein level both in rat and human gastrointestinal tract. The presence of bNOS in nerve tissue supports previous observations that NO serves as a transmitter in non-adrenergic, non-cholinergic nerves in human esophagus and stomach. The observation that ecNOS has been found mainly in endothelial cells suggests the involvement of NO in the regulation of mucosal blood flow. (+info)