Metoclopramide does not increase gastric muscle contractility in newborn rats

2014 ◽  
Vol 306 (5) ◽  
pp. G439-G444 ◽  
Author(s):  
Moshe Yair Kasirer ◽  
Christopher Welsh ◽  
Jingyi Pan ◽  
Yulia Shifrin ◽  
Jaques Belik

Feeding intolerance resulting from delayed gastric emptying is common in premature neonates. Metoclopramide (MCP), the most frequently used prokinetic drug in neonates, enhances gastric muscle contractility through inhibition of dopamine receptors. Although its therapeutic benefit is established in adults, limited data are available to support its clinical use in infants. Hypothesizing that developmentally dependent differences are present, we comparatively evaluated the effect of MCP on fundus muscle contractility in newborn, juvenile, and adult rats. The muscle strips were either contracted with electrical field stimulation (EFS) to induce cholinergic nerve-mediated acetylcholine release or carbachol, a cholinergic agonist acting directly on the muscarinic receptor. Although in adult rats MCP increased EFS-induced contraction by 294 ± 122% of control ( P < 0.01), no significant effect was observed in newborn fundic muscle. MCP had no effect on the magnitude of the carbachol-induced and/or bethanechol-induced gastric muscle contraction at any age. In response to dopamine, an 80.7 ± 5.3% relaxation of adult fundic muscle was observed, compared with only a 8.4 ± 8.7% response in newborn tissue ( P < 0.01). Dopamine D2 receptor expression was scant in neonates and significantly increased in adult gastric tissue ( P < 0.01). In conclusion, the lack of MCP effect on the newborn fundic muscle contraction potential relates to developmental differences in dopamine D2 receptor expression. To the extent that these novel data can be extrapolated to neonates, the therapeutic value of MCP as a prokinetic agent early in life requires further evaluation.

1997 ◽  
Vol 273 (2) ◽  
pp. G456-G463 ◽  
Author(s):  
M. C. Baccari ◽  
C. Iacoviello ◽  
F. Calamai

The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L-NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2 alpha), or carbachol (CCh), a fast relaxant response that, depending on stimulation frequency and strip tension, could be followed by a slower, sustained relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations and often reversed them into contractions; these effects were greatly counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to block the EFS-induced fast relaxations as the CCh concentration was increased. The NO synthesis inhibitors greatly reduced the sustained relaxant responses elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The results indicate that the NO synthesis inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway. The involvement of both VIP and NO in sustained relaxations is also suggested.


Neuroscience ◽  
2016 ◽  
Vol 330 ◽  
pp. 50-56 ◽  
Author(s):  
S. Lakehayli ◽  
N. Said ◽  
M. El Khachibi ◽  
M. El Ouahli ◽  
S. Nadifi ◽  
...  

2013 ◽  
Vol 305 (1) ◽  
pp. G47-G57 ◽  
Author(s):  
Christopher Welsh ◽  
Masahiro Enomoto ◽  
Jingyi Pan ◽  
Yulia Shifrin ◽  
Jaques Belik

Pyloric stenosis, the most common infant gastrointestinal disease, has no known etiology and clinically presents as abnormal gastric emptying with evidence of pyloric muscle hypertrophy. Whether abnormalities in gastric muscle contraction and/or relaxation have a role in this condition is poorly known, but gastroparesis is commonly observed in association with delayed gastric emptying in adults. Therefore, we evaluated the tetrahydrobiopterin (BH4)-deficient newborn mouse model of this disease ( hph-1) and hypothesized that their gastric muscle properties are impaired, when compared with wild-type control animals. In vitro studies evaluating the age-dependent gastric fundus muscle contraction and relaxation potential were conducted. Compared with wild-type mice, the hph-1 stomach content/body weight ratio was significantly increased in newborn but not juvenile or adult animals, confirming abnormal gastric emptying. Gastric tissue neuronal nitric oxide synthase (nNOS) protein expression was upregulated in both newborn and adult hph-1 mice, but in the former there was evidence of enzyme uncoupling and higher tissue superoxide generation when compared with same age-matched animals. As opposed to the lack of strain differences in the U46619-induced force, the newborn hph-1 gastric muscle carbachol-induced contraction and nNOS-dependent relaxation were significantly reduced ( P < 0.01). These group differences were not present in juvenile or adult mice. Preincubation with BH4 significantly enhanced the newborn hph-1, but not wild-type, gastric muscle contraction. In conclusion, changes compatible with gastroparesis are present in the newborn mouse model of pyloric stenosis. The role of BH4 deficiency and possibly associated gastroparesis in the pathogenesis of infantile pyloric stenosis warrants further investigation.


2017 ◽  
Vol 24 (2) ◽  
pp. 193-205 ◽  
Author(s):  
Lindsey R. Hammerslag ◽  
Amogh P. Belagodu ◽  
Olubankole A. Aladesuyi Arogundade ◽  
Angela G. Karountzos ◽  
Qingrou Guo ◽  
...  

2015 ◽  
Vol 13 (2) ◽  
pp. 10-13 ◽  
Author(s):  
Marat Igorevich Airapetov ◽  
Platon Platonovich Khokhlov ◽  
Eugeny Rudolfovich Bychkov ◽  
Edgar Arturovich Sekste ◽  
Natalia Dmitrievna Yakushina ◽  
...  

The purpose of the paper was to study both the desacylghrelin (unacylated ghrelin) level in the blood serum and expression of mRNA ghrelin receptor in the brain structures in ontogeny after chronic alcoholization in rats. The results proved that the prenatal effect of ethanol negatively affected the maturation of dopaminergic and ghrelin systems of the brain as well as involvement of ghrelin system in mechanisms of alcohol dependence formation. The decrease of COMT mRNA expression simultaneoully with the increase of expression of D2 long and short isoforms of dopaminergic receptors and misbalance of ghrelin system were observed. Alcoholization of mothers reduced desacylghrelin level in the blood serum in early postnatal period in offsprings although mRNA expression of ghrelin receptor in the brain was elevated. Chronic alcoholization of adult rats also affected the ghrelin system. In the alcoholiztion process, the reduced contents of desacylghrelin in the blood serum with compensatory increase of ghrelin receptor expression in the brain were registered. After withdrawal of ethanol, the recovery of desacylghrelin level (tendency to normalization) was observed.


2009 ◽  
Vol 1 (1) ◽  
pp. 45-53
Author(s):  
Manuel García ◽  
Hernandes Corralho

The prostate gland is regulated by steroid hormones and complex interactions based on a subtle balance between androgen and estrogen (E2) regulate prostatic development and physiology. Interestingly, the changes in steroid hormone levels at old ages affect the hormonal milieu and contribute to the evolution of the pathological changes of the gland. We have analyzed the effects of letrozole, an aromatase inhibitor, on the structure in the ventral prostate of control and castrated adult rats. The results demonstrated alterations in prostate physiology after letrozole treatment. Serum levels of testosterone, prostate weight and proliferative index in luminal and basal cells were increased. Estrogen serum levels were not altered dramatically, in contrast to slight increase in gonadotrophin hormones seen in the castrated animals. Castration did not alter the proliferation index of basal cells. Reorganization of tissue compartments was seen with significant increase in letrozole treated animals. A decrease in androgen receptor expression was seen 21-days after the beginning of treatment with letrozole. These results were confirmed by immunohistochemistry. These results reveal new aspects in the relationship between androgen receptor and steroid metabolism in the prostate gland, demonstrating that alteration in hormone levels during a short time period induces significant alterations in prostate homeostasis. 


2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Jianqing Zhu ◽  
Zhanying Qi ◽  
Chaohui Lin

Objective: To investigate the water extract from Radix (Flemingia philippinensis Merr et Rolfe Decoction.) Effect of sciatic nerve gastrocnemius muscle Characteristics of isolated frog. Methods: The dissected lesion of sciatic nerve gastrocnemius muscle was infused with 0.9% saline, 0.125g / mL, 0.25g / mL, 0.5g / mL jelly extract, and the RM6240 bio-signal collector was used to measure each The infiltration depth of 5 minutes, infiltration for 10 minutes, infiltration of 15 minutes at each time point of the gastrocnemius muscle contraction threshold strength (measured at each time point 5 times) and complete single contraction curve (measured at each time point 25) Systolic rate, systolic rate, rate of contraction, and latency. Results: The systolic threshold intensity of the gastrocnemius muscle increased with the increase of the concentration of the extraction fluid, but less than the pre-treatment level (P <0.01, P <0.05). If the concentration and time (P <0.05). At the same time, the systolic amplitude, systolic rate and diastolic rate increased first and then decreased with the increase of the concentration of the extract (P <0.01, P <0.05). The latency of the sciatic nerve of the sciatic nerve was affected by the concentration of the drug in the infiltration solution, which decreased first and then increased with the increase of the drug concentration. Conclusion: The systolic characteristics of skeletal muscle are affected by the weight of the components. Low concentration of salt water extract in a short time to improve the ability of skeletal muscle contraction, treatment time is too long or too high concentration of crude drugs will make the skeletal muscle contractility weakened, and even inhibit the skeletal muscle contractility, and affect the nerve Muscle excitement signal transmission.


2017 ◽  
Author(s):  
Lindsey Robertson Hammerslag ◽  
Amogh P. Belagodu ◽  
Olubankole Aladesuyi ◽  
Angela G. Karountzos ◽  
Qingrou Guo ◽  
...  

Impulsivity is a personality trait associated with a heightened risk for drug use and other psychiatric conditions. Because impulsivity-related disorders typically emerge during adolescence, there has been interest in exploring methods for identifying adolescents that will be at risk to develop substance use disorders in adulthood. Here, we used a rodent model to assess inhibitory control (impulsive action) and impulsive decision making (impulsive choice) during adolescence (43-50 days old) or adulthood (93-100 days old) and then examined the impact of development on these impulsivity traits by retesting rats 50 days later. Impulsive action was not stable from adolescence to adulthood in males and was lowest in adult males, relative to adolescents and females. Impulsive choice was stable across development and unaffected by age or sex. Next, we examined the connection between our model of impulsivity and two measures relevant to substance abuse research: the initiation of voluntary alcohol drinking and dopamine D2 receptor (D2R) expression in the prelimbic prefrontal cortex. Consumption of saccharin-sweetened ethanol during 30 min sessions in adulthood was associated with adolescent, but not adult, impulsive action, particularly in males. Prelimbic D2R expression was reduced in individuals with high levels of impulsive choice and this relationship appeared to be strongest among females. The results of this study demonstrate that impulsive choice, along with its connection to D2R expression, is relatively unchanged by the process of development. For impulsive action however, individual levels of impulsivity during adolescence predict drinking in adulthood despite changes in the measure during development.


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