scholarly journals Peripheral and central actions of orphanin FQ (nociceptin) on murine colon

1999 ◽  
Vol 276 (1) ◽  
pp. G125-G131 ◽  
Author(s):  
M. A. Osinski ◽  
P. Bass ◽  
E. A. Gaumnitz
Keyword(s):  
Contractile Activity ◽  
Gastrointestinal Transit ◽  
Colonic Transit ◽  
Peptide Ligand ◽  
Orphanin Fq ◽  
Endogenous Opioid ◽  
Intracerebroventricular Injections ◽  
Central Actions ◽  
Murine Colon

Orphanin FQ (OFQ), also known as nociceptin, is a recently isolated endogenous peptide with a structure similar to the endogenous opioid peptides. The present study examines the actions of centrally administered OFQ on in vivo murine gastrointestinal and colonic transit as well as the actions of OFQ on the isolated colon. Intracerebroventricular injections of OFQ dose dependently inhibited colonic propulsive activity. OFQ inhibition of colonic propulsion was unaffected by coadministration of the competitive opioid receptor antagonist naltrexone. A subadditive response was observed when approximately equipotent doses of either morphine sulfate or the δ-agonist DPDPE were coadministered with OFQ. No subadditivity was observed with coadministration of the μ-agonist DAMGO, suggesting a functional interaction between OFQ and δ-opioid central pathways regulating colonic transit. High, but not low, doses of OFQ also inhibited the transit of a nonabsorbable charcoal marker through the stomach and/or small intestine. OFQ potently contracted isolated colon preparations; contractile activity was abolished by TTX or chlorpromazine. Our results suggest that OFQ may be an important peptide ligand acting on a novel inhibitory neural pathway that modulates gastrointestinal transit.

scholarly journals Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4993-5001 ◽  
Author(s):  
Chad D. Foradori ◽  
Marcel Amstalden ◽  
Lique M. Coolen ◽  
Sushma R. Singh ◽  
Christine J. McManus ◽  
...  
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Brain Regions ◽  
Orphanin Fq ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
External Zone ◽  
Gnrh Secretion

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg14, Lys15] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.

scholarly journals Genetic deletion of trkB.T1 increases neuromuscular function

2012 ◽  
Vol 302 (1) ◽  
pp. C141-C153 ◽  
Author(s):  
Susan G. Dorsey ◽  
Richard M. Lovering ◽  
Cynthia L. Renn ◽  
Carmen C. Leitch ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Calcium Release ◽  
Contractile Activity ◽  
Muscle Tension ◽  
Neuromuscular Synapse ◽  
Neuromuscular Function ◽  
In Vitro Assays ◽  
Tyrosine Kinase Receptor ◽  
Akt Activation

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.

scholarly journals Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility

2019 ◽  
Vol 141 (3) ◽  
Author(s):  
Alexander W. Caulk ◽  
Jay D. Humphrey ◽  
Sae-Il Murtada
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Function ◽  
Contractile Function ◽  
Contractile Activity ◽  
Comparison Of Methods ◽  
Axial Stretch ◽  
Smooth Muscle Function ◽  
In Vivo Loading

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation

1995 ◽  
Vol 269 (2) ◽  
pp. E283-E289 ◽  
Author(s):  
A. K. Saha ◽  
T. G. Kurowski ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Plasma Insulin ◽  
Contractile Activity ◽  
High Plasma ◽  
Muscle Contractions ◽  
Glucose Levels ◽  
Malonyl Coa ◽  
Ad Libitum ◽  
Sciatic Nerve Stimulation

Increases in the concentration of malonyl-CoA in skeletal muscle have been observed in the KKAy mouse, an obese rodent with high plasma insulin and glucose levels [Saha et al. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E95-E101, 1994]. To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 +/- 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 +/- 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA levels were 1.3 +/- 0.1, 1.8 +/- 0.1, or 2.4 +/- 0.2 nmol/g, respectively, in the absence of insulin and 1.7 +/- 0.1, 4.6 +/- 0.3, or 5.5 +/- 0.6 nmol/g in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA was increased threefold in the soleus 6-8 h after denervation and remained twofold higher for > or = 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30-35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vivo Pain-Inhibitory Role of Nociceptin/Orphanin FQ in Spinal Cord

2003 ◽  
Vol 305 (2) ◽  
pp. 495-501 ◽  
Author(s):  
Makoto Inoue ◽  
Toshiko Kawashima ◽  
Hiroshi Takeshima ◽  
Girolamo Calo ◽  
Atsuko Inoue ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Orphanin Fq ◽  
Inhibitory Role

scholarly journals Phenotypic Traits and Immunomodulatory Properties of Leuconostoc carnosum Isolated From Meat Products

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefano Raimondi ◽  
Gloria Spampinato ◽  
Francesco Candeliere ◽  
Alberto Amaretti ◽  
Paola Brun ◽  
...  
Keyword(s):  
Meat Products ◽  
Gastrointestinal Transit ◽  
Antibiotic Resistance Genes ◽  
Protective Role ◽  
Phenotypic Traits ◽  
Natural Habitats ◽  
Genes Encoding ◽  
Immunomodulatory Properties ◽  
Leuconostoc Carnosum

Twelve strains of Leuconostoc carnosum from meat products were investigated in terms of biochemical, physiological, and functional properties. The spectrum of sugars fermented by L. carnosum strains was limited to few mono- and disaccharides, consistently with the natural habitats of the species, including meat and fermented vegetables. The strains were able to grow from 4 to 37°C with an optimum of approximately 32.5°C. The ability to grow at temperatures compatible with refrigeration and in presence of up to 60 g/L NaCl explains the high loads of L. carnosum frequently described in many meat-based products. Six strains produced exopolysaccharides, causing a ropy phenotype of colonies, according to the potential involvement on L. carnosum in the appearance of slime in packed meat products. On the other side, the study provides evidence of a potential protective role of L. carnosum WC0321 and L. carnosum WC0323 against Listeria monocytogenes, consistently with the presence in these strains of the genes encoding leucocin B. Some meat-based products intended to be consumed without cooking may harbor up to 108 CFU/g of L. carnosum; therefore, we investigated the potential impact of this load on health. No strains survived the treatment with simulated gastric juice. Three selected strains were challenged for the capability to colonize a mouse model and their immunomodulatory properties were investigated. The strains did not colonize the intestine of mice during 10 days of daily dietary administration. Intriguingly, despite the loss of viability during the gastrointestinal transit, the strains exhibited different immunomodulatory effect on the maturation of dendritic cells in vivo, the extent of which correlated to the production of exopolysaccharides. The ability to stimulate the mucosal associated immune system in such probiotic-like manner, the general absence of antibiotic resistance genes, and the lack of the biosynthetic pathways for biogenic amines should reassure on the safety of this species, with potential for exploitation of selected starters.

scholarly journals {Ru(CO)x}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

2017 ◽  
Vol 46 (9) ◽  
pp. 3025-3040 ◽  
Author(s):  
Gabriella Tamasi ◽  
Antonello Merlino ◽  
Federica Scaletti ◽  
Petra Heffeter ◽  
Anton A. Legin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Anticancer Activity ◽  
Antitumor Effects ◽  
X Ray ◽  
Murine Colon

fac-[RuII(CO)3Cl2(MBI)] and -[RuII(CO)3Cl2(DMBI)] are CO-releasing materials able to link histidines of proteins, and the latter showed antitumor effects in murine colon cancer.

Skeletal muscle phenotype signaling with ex vivo endurance-type dynamic contractions in rat muscle

2021 ◽  
Author(s):  
Jesper Emil Jakobsgaard ◽  
Jacob Andresen ◽  
Frank V. de Paoli ◽  
Kristian Vissing
Keyword(s):  
Skeletal Muscle ◽  
Translation Initiation ◽  
Ex Vivo ◽  
Contractile Activity ◽  
Specific Protein ◽  
Signaling Proteins ◽  
Dependent Manner ◽  
Metabolic Signaling ◽  
Dynamic Endurance

Skeletal muscle phenotype may influence the response sensitivity of myocellular regulatory mechanisms to contractile activity. To examine this, we employed an ex vivo endurance-type dynamic contraction model to evaluate skeletal muscle phenotype-specific protein signaling responses in rat skeletal muscle. Preparations of slow-twitch soleus and fast-twitch extensor digitorum longus skeletal muscle from 4-wk old female Wistar rats were exposed to an identical ex vivo dynamic endurance-type contraction paradigm consisting of 40 minutes of stretch-shortening contractions under simultaneous low-frequency electrostimulation delivered in an intermittent pattern. Phosphorylation of proteins involved in metabolic signaling and signaling for translation initiation was evaluated at 0, 1, and 4 hours after stimulation by immunoblotting. For both muscle phenotypes, signaling related to metabolic events was upregulated immediately after stimulation, with concomitant absence of signaling for translation-initiation. Signaling for translation-initiation was then activated in both muscle phenotypes at 1-4 hours after stimulation, coinciding with attenuated metabolic signaling. The recognizable pattern of signaling responses support how our ex vivo dynamic muscle contraction model can be utilized to infer a stretch-shortening contraction pattern resembling stretch-shortening contraction of in vivo endurance exercise. Moreover, using this model, we observed that some specific signaling proteins adhering to metabolic events or to translation initation exhibited phosphorylation changes in a phenotype-dependent manner, whereas other signaling proteins exhibited phenotype-independent changes. These findings may aid the interpretation of myocellular signaling outcomes adhering to mixed muscle samples collected during human experimental trials.

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