Vagal influence on gastroduodenal HCO3- secretion in the cat in vivo

1987 ◽  
Vol 252 (4) ◽  
pp. G522-G528 ◽  
Author(s):  
O. Nylander ◽  
G. Flemstrom ◽  
D. Delbro ◽  
L. Fandriks
Keyword(s):  
Electrical Stimulation ◽  
Muscarinic Receptors ◽  
Fold Increase ◽  
Vagal Nerves ◽  
Alkaline Secretion ◽  
Gastric Secretions ◽  
Distal Direction ◽  
Vagal Influence

Gastric and duodenal secretions of HCO3- were studied simultaneously in chloralose-anesthetized cats. The adrenals were ligated, and the cervical vagal as well as the abdominal splanchnic nerves were cut. Gastric secretions of H+ and HCO3- were calculated from measurements of the pH and PCO2 in the luminal perfusate. A duodenal segment devoid of Brunner's glands and pancreaticobilary secretions was cannulated in situ and the alkaline secretion determined by continuous titration at luminal pH 7.4. Electrical stimulation in the distal direction for 10–15 min of the cervical vagal nerves resulted in a 6- to 10-fold increase in gastric H+ and in a 20–60% rise in gastric HCO-3 secretion. Duodenal HCO3- secretion increased by 65–155%. Gastric basal secretions of H+ and HCO3- were not affected by atropine or hexamethonium, but both agents inhibited basal duodenal HCO3- secretion. Hexamethonium abolished and atropine reduced the rise in all secretions in response to vagal nerve stimulation. Thus gastroduodenal mucosal HCO3- secretion is stimulated by vagal mechanisms involving action on nicotinic as well as on muscarinic receptors and possibly also noncholinergic neurotransmission.

Abstract 33: Unlocking Reprogramming Capability: Silencing Antiplasticity Gene p63 Enhances the Reprogramming of Fibroblasts into Induced Cardiomyocytes

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Vivekkumar Patel ◽  
Austin Cooney ◽  
Elsa Flores ◽  
Vivek Singh ◽  
Megumi Mathison ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Troponin T ◽  
Cardiac Fibroblasts ◽  
Fold Increase ◽  
Cellular Reprogramming ◽  
Embryonic Fibroblasts ◽  
Reprogramming Efficiency ◽  
Cardiac Transcription Factors

Objective: In situ cellular reprogramming of cardiac fibroblasts into (induced) cardiomyocytes (iCMs) represents a promising new potential intervention for the treatment of heart failure. Despite encouraging in vivo data in rodent myocardial infarction models, the relative resistance of human cells to reprogramming may be a significant barrier to the clinical application of this new therapy. We hypothesized that knockdown of the anti-plasticity gene p63 could therefore be used to enhance cellular reprogramming efficiency. Methods: p63 knockout (KO) murine embryonic fibroblasts (MEFs) and MEFs treated with p63 silencing shRNA were assessed for expression of the cardiomyocyte marker Cardiac Troponin T (cTnT) and pro-cardiogenic genes, with or without the treatment with known cardiac transcription factors Hand2 and Myocardin (HM). Results: After 3 wks in culture, expression of the cardiomyocyte marker cTnT (FACS) was significantly greater in p63 KO MEFs than in wild-type (WT) MEFs or WT MEFs treated with transcription factors Hand2 and Myocardin (39% ± 8%, 2.0% ± 1% and 2.7 ± 0.3%, respectively, p < 0.05). Treatment of p63 KO MEFs with Hand2 and Myocardin further increased cTnT expression up to 74% ± 3%. Treatment of WT MEFs with p63 shRNA likewise yielded a 20-fold increase in cTnT expression (qPCR) without HM and a 600-fold increase with HM when compared to non-silencing shRNA treated MEFs. Consistent with these findings, p63 KO or p63 shRNA-treated MEFs demonstrated increased expression (qPCR) of pro-cardiogenic genes Gata4, Mef2c and Tbx5 compared to naïve or non-silencing shRNA treated MEFs. After treatment with p63 shRNA, adult human epidermal cells also demonstrated increased expression of cTnT, myosin heavy chain and pro-cardiogenic genes when analyzed by qPCR. Conclusions: Downregulation of the anti-plasticity gene p63 enhances cellular reprogramming efficiency and iCM generation, as reflected in the increased expression of the cardiomyocyte marker cTnT and pro-cardiogenic genes Gata4, Mef2c and Tbx5. Use of such cellular plasticity enhancing strategies may be a useful strategy to overcome barriers to cellular reprogramming in the clinical arena.

scholarly journals Characterization of Prejunctional Muscarinic Receptors: Effects on the Release of VIP and Functional Responses and Receptor Expression in the Ovine Submandibular Gland

2009 ◽  
Vol 2009 ◽  
pp. 1-6
Author(s):  
Anders T. Ryberg ◽  
Ondrej Soukup ◽  
Gunnar Tobin
Keyword(s):  
Electrical Stimulation ◽  
Submandibular Gland ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Chorda Tympani Nerve ◽  
Functional Responses ◽  
Stimulation Of

In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

In vivo modulation by α2-adrenoceptors of adrenal catecholamine release in the anaesthetized dog

1988 ◽  
Vol 66 (3) ◽  
pp. 380-384 ◽  
Author(s):  
Sylvain Foucart ◽  
Jacques de Champlain ◽  
Reginald Nadeau
Keyword(s):  
Electrical Stimulation ◽  
Splanchnic Nerve ◽  
Catecholamine Release ◽  
Agonist Stimulation ◽  
Control Stimulation ◽  
Anaesthetized Dog ◽  
Splanchnic Nerve Stimulation ◽  
Stimulation Of

In this study, the reversal of the potentiating effect of idazoxan, a selective α2-antagonist, on adrenal catecholamine release elicited by splanchnic nerve stimulation in anaesthetized and vagotomized dogs, was investigated with the use of oxymetazoline, a selective α2-agonist. Stimulation of the left splanchnic nerve (5.0-V pulses of 2 ms duration for 3 min at a frequency of 2 Hz) was applied before and 20 min after the i. v. injection of each drug. Blood samples were collected in the adrenal vein before and at the end of each stimulation. The results show that the release of catecholamines induced by electrical stimulation was potentiated by 50% after idazoxan injection (0.1 mg/kg). This enhanced response was significantly antagonized by the subsequent injection of oxymetazoline (2 μg/kg). The α2-modulating effect appears to be related to the amount of catecholamines released during the stimulation, since by subgrouping of the data on the basis of the degree of potentiation by idazoxan, it was observed that this drug was more efficient when catecholamine release was higher during control stimulation. In contrast, the reversing effect of oxymetazoline was found to be more pronounced when catecholamine release was lower. These results thus suggest that the sensitivity of the α2-adrenoceptor mechanism may depend upon the in situ concentration of adrenal catecholamine release during electrical stimulation and that the potentiating effect of α2-blockade can be reversed by activation of those receptors by a selective α2-agonist.

scholarly journals The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Antje M. Wengner ◽  
Simon C. Pitchford ◽  
Rebecca C. Furze ◽  
Sara M. Rankin
Keyword(s):  
Bone Marrow ◽  
Intraperitoneal Injection ◽  
Fold Increase ◽  
In Situ Perfusion ◽  
Acute Peritonitis ◽  
Femoral Bone Marrow ◽  
Prior Administration

In this study, we have identified a unique combinatorial effect of the chemokines KC/MIP-2 and the cytokine granulocyte colony-stimulating factor (G-CSF) with respect to the rapid mobilization of neutrophils from the bone marrow in a model of acute peritonitis. At 2 hours following an intraperitoneal injection of thioglycollate, there was a 4.5-fold increase in blood neutrophil numbers, which was inhibited 84% and 72% by prior administration of blocking mAbs against either the chemokines KC/MIP-2 or G-CSF, respectively. An intraperitoneal injection of G-CSF acted remotely to stimulate neutrophil mobilization, but did not elicit recruitment into the peritoneum. Further, in vitro G-CSF was neither chemotactic nor chemokinetic for murine neutrophils, and had no priming effect on chemotaxis stimulated by chemokines. Here, we show that, in vitro and in vivo, G-CSF induces neutrophil mobilization by disrupting their SDF-1α–mediated retention in the bone marrow. Using an in situ perfusion system of the mouse femoral bone marrow to directly assess mobilization, KC and G-CSF mobilized 6.8 × 106 and 5.4 × 106 neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 × 106 neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization.

The effect of amitriptyline, mianserin, and viloxazine at pre- and post-junctional muscarinic receptors in guinea-pig ileal longitudinal muscle

1982 ◽  
Vol 60 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Y. H. Kwok ◽  
F. Mitchelson
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Longitudinal Muscle ◽  
Fold Increase ◽  
Selective Inhibition

The antimuscarinic activity of amitriptyline, mianserin, and viloxazine was compared with atropine in guinea-pig ileal longitudinal muscle. The pA2 values obtained using carbachol (CCh) as agonist were as follows: atropine, 9.55; amitriptyline, 7.50; mianserin, 6.40; and viloxazine, 4.91. Responses to transmural electrical stimulation (1–50 Hz) were more resistant than those produced by CCh to inhibition by atropine and the antidepressants. This did not appear to be due to a selective inhibition of prejunctional inhibitory muscarinic receptors, as a pA2 of 8.73 was obtained with atropine for the depression of oxotremorine-induced inhibition of acetylcholine (ACh) output. Amitriptyline (10 μM) caused a 2.4-fold increase in ACh output and was 200-fold weaker than atropine at doubling ACh output in the longitudinal muscle stimulated at 0.3 Hz. Mianserin (10 μM) and viloxazine (1–10 μM) did not significantly affect ACh output. It is suggested that the antidepressants exhibit a greater affinity for the postjunctional muscarinic receptors in the guinea-pig ileal longitudinal muscle.

scholarly journals Co-expression With Replicating Vector Overcoming Competitive Effects Derived by a Companion Protease Inhibitor in Plants

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiexue Ma ◽  
Xiangzhen Ding ◽  
Zhiying Li ◽  
Sheng Wang
Keyword(s):  
Protease Inhibitor ◽  
Molecular Farming ◽  
Expression System ◽  
Fold Increase ◽  
Protective Effects ◽  
Competitive Effects ◽  
Inoculum Dose ◽  
Plant Expression Systems

Plant-based expression platforms are currently gaining acceptance as a viable alternative for the production of recombinant proteins (RPs), but the degradation of RPs by proteases in cells hinders their superb potentials. Co-expression of a protease inhibitor (PI) shows promise as a strategy to prevent RP from proteolytic degradation in plants. However, competitive effects behind the PI-RP co-expression system may mask or obfuscate the in situ protective effects of a companion PI. Here, we explored the competitive effects by co-expressing reteplase (rPA) with three unrelated PIs, namely NbPR4, HsTIMP, and SlCYS8, in Nicotiana benthamiana leaves. Remarkably, the accumulation of rPA was significantly repressed by each of the three PIs, suggesting that the competitive effects may be common among the PIs. The repression can be attenuated by reducing the PI inoculum dose in the co-inoculation mixtures, showing a negative correlation between the PI abundance of the PI-RP system and competitive effects. Interestingly, when a replicating vector was used to modulate the relative abundance of PI and RP in vivo, rPA was still boosted even at the maximal testing dose of PI, indicating that the competitive effects reduced to an ignorable level by this in vivo approach. Furthermore, a 7- to 12-fold increase of rPA was achieved, proving that it is a useful way for stimulating the potentials of a companion PI by overcoming competitive effects. And, this approach can be applied to molecular farming for improving the RP yields of plant expression systems.

Effects of hypovolemia on blood flow, arterial [HCO3-], and HCO3- output in the rat duodenum

1990 ◽  
Vol 259 (2) ◽  
pp. G179-G183 ◽  
Author(s):  
C. Jonson ◽  
L. Holm ◽  
T. Jansson ◽  
L. Fandriks
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Treated Group ◽  
Similar Extent ◽  
Anesthetized Rats ◽  
Vagal Nerves ◽  
Group A ◽  
Rat Duodenum ◽  
Alkaline Secretion

The effects of bleeding-induced hypovolemia on duodenal blood flow (microsphere technique), arterial [HCO3-], and duodenal HCO3- secretion (in situ titration) were investigated in chloralose-anesthetized rats. A 10% decrease in blood volume reduced duodenal HCO3- secretion by 44%, duodenal blood flow by 31%, and arterial [HCO3-] by 11%. In a group with cervically cut vagal nerves, basal duodenal HCO3- secretion was greater than 50% lower compared with controls. Basal blood flow and arterial [HCO3-] were on similar levels as in nonvagotomized animals. Furthermore, bleeding failed to lower duodenal alkaline output in rats with cut vagal nerves, although blood flow and arterial [HCO3-] were reduced to a similar extent as in the vagally intact controls. In a yohimbine-treated group, a 10% bleeding reduced duodenal blood flow by 28% and arterial [HCO3-] by 7% without influencing duodenal HCO3- secretion. We suggest that the hypovolemia-induced inhibition of duodenal alkaline secretion is not caused by a decrease in blood and/or arterial [HCO3-]. Instead, other factors may be of importance, for example, neural effects on enteric secretomotor neurons or directly on the secreting epithelium.

scholarly journals Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing

2017 ◽  
Vol 114 (32) ◽  
pp. E6490-E6497 ◽  
Author(s):  
Samantha M. Sarett ◽  
Thomas A. Werfel ◽  
Linus Lee ◽  
Meredith A. Jackson ◽  
Kameron V. Kilchrist ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Xenograft Model ◽  
Fold Increase ◽  
Cell Uptake ◽  
Orthotopic Model ◽  
Pharmacokinetic Properties ◽  
Carrier Free ◽  
Tumor Accumulation

Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers by leveraging the long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized siRNA conjugated to a diacyl lipid moiety (siRNA-L2), which rapidly binds albumin in situ. siRNA-L2, in comparison with unmodified siRNA, exhibited a 5.7-fold increase in circulation half-life, an 8.6-fold increase in bioavailability, and reduced renal accumulation. Benchmarked against leading commercial siRNA nanocarrier in vivo jetPEI, siRNA-L2 achieved 19-fold greater tumor accumulation and 46-fold increase in per-tumor-cell uptake in a mouse orthotopic model of human triple-negative breast cancer. siRNA-L2 penetrated tumor tissue rapidly and homogeneously; 30 min after i.v. injection, siRNA-L2 achieved uptake in 99% of tumor cells, compared with 60% for jetPEI. Remarkably, siRNA-L2 achieved a tumor:liver accumulation ratio >40:1 vs. <3:1 for jetPEI. The improved pharmacokinetic properties of siRNA-L2 facilitated significant tumor gene silencing for 7 d after two i.v. doses. Proof-of-concept was extended to a patient-derived xenograft model, in which jetPEI tumor accumulation was reduced fourfold relative to the same formulation in the orthotopic model. The siRNA-L2 tumor accumulation diminished only twofold, suggesting that the superior tumor distribution of the conjugate over nanoparticles will be accentuated in clinical situations. These data reveal the immense promise of in situ albumin targeting for development of translational, carrier-free RNAi-based cancer therapies.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

1996 ◽  
Vol 54 ◽  
pp. 288-289
Author(s):  
Greg V. Martin ◽  
Ann L. Hubbard
Keyword(s):  
Three Dimensional ◽  
Integral Membrane Proteins ◽  
Polarized Secretion ◽  
Microscope Images ◽  
Computer Aided ◽  
Intracellular Organelles ◽  
Cytoskeletal Elements ◽  
Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

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