The effect of coniine on presynaptic nicotinic receptors

2016 ◽  
Vol 71 (5-6) ◽  
pp. 115-120 ◽  
Author(s):  
Ulkem Erkent ◽  
Alper B. Iskit ◽  
Rustu Onur ◽  
Mustafa Ilhan
Keyword(s):  
Guinea Pig ◽  
Nicotinic Receptor ◽  
Nicotinic Receptors ◽  
Clinical Signs ◽  
Toxicological Effects ◽  
Conium Maculatum ◽  
Anococcygeus Muscle ◽  
Rat Anococcygeus Muscle

Abstract Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (–logIC50 = 3.79 ± 0.11 and –logIC50 = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (–logIC50 = 4.47 ± 0.12 M) and did not differ from the –logIC50 value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Role of intrapancreatic ganglia in regulation of periodic insular secretions

1985 ◽  
Vol 248 (5) ◽  
pp. E522-E530 ◽  
Author(s):  
J. I. Stagner ◽  
E. Samols
Keyword(s):  
Insulin Release ◽  
Nicotinic Receptor ◽  
Nicotinic Receptors ◽  
Regulatory System ◽  
Oscillatory Pattern ◽  
Adrenergic Antagonists ◽  
Alpha Bungarotoxin ◽  
Pancreatic Hormone

The regulatory system responsible for insulin oscillations from the in vitro pancreas is unknown. To test the hypothesis that intrapancreatic ganglia are the pacemaker or driver of the oscillations, combined nicotinic, muscarinic, and adrenergic antagonists were infused. Combined muscarinic, alpha- and beta-adrenergic, and presynaptic nicotinic receptor blockade (beta-bungarotoxin) was without effect on oscillations. The infusion of the postsynaptic nicotinic receptor antagonists, hexamethonium, alpha-bungarotoxin (ATX), or curarine, significantly altered the preinfusion oscillatory pattern of insulin release by reducing the period. Nicotine-stimulated insulin release was inhibited by ATX on a background of atropine, phentolamine, and beta-bungarotoxin. Propranolol decreased nicotine-stimulated insulin release, which was further reduced by ATX. These data support the theory that nicotinic receptors may be present pre- and postsynaptically at the ganglionic level and presynaptically on sympathetic nerve axons. We propose that ganglionic nicotinic receptors may be regulatory and that ganglia may serve as the pacemaker to regulate pancreatic hormone oscillations.

scholarly journals Importance and Antimicrobial Resistance of Mycoplasma bovis in Clinical Respiratory Disease in Feedlot Calves

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1470
Author(s):  
Ana García-Galán ◽  
Juan Seva ◽  
Ángel Gómez-Martín ◽  
Joaquín Ortega ◽  
Francisco Rodríguez ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Clinical Signs ◽  
Antimicrobial Treatment ◽  
Mycoplasma Bovis ◽  
Bacterial Disease ◽  
Feedlot Calves ◽  
Fixed Panel

Bovine respiratory disease (BRD) is an important viral and/or bacterial disease that mainly affects feedlot calves. The involvement of Mycoplasma bovis in BRD can lead to chronic pneumonia poorly responsive to antimicrobial treatment. Caseonecrotic bronchopneumonia is a pulmonary lesion typically associated with M. bovis. In Spain, M. bovis is widely distributed in the feedlots and circulating isolates are resistant to most antimicrobials in vitro. However, the role of this species in clinical respiratory disease of feedlot calves remains unknown. Furthermore, available data are relative to a fixed panel of antimicrobials commonly used to treat BRD, but not to the specific set of antimicrobials that have been used for treating each animal. This study examined 23 feedlot calves raised in southeast Spain (2016–2019) with clinical signs of respiratory disease unresponsive to treatment. The presence of M. bovis was investigated through bacteriology (culture and subsequent PCR), histopathology and immunohistochemistry. The pathogen was found in 86.9% (20/23) of the calves, mainly in the lungs (78.26%; 18/23). Immunohistochemistry revealed M. bovis antigens in 73.9% (17/23) of the calves in which caseonecrotic bronchopneumonia was the most frequent lesion (16/17). Minimum inhibitory concentration assays confirmed the resistance of a selection of 12 isolates to most of the antimicrobials specifically used for treating the animals in vivo. These results stress the importance of M. bovis in the BRD affecting feedlot calves in Spain.

Protective role of epithelium in the guinea pig airway

1989 ◽  
Vol 66 (4) ◽  
pp. 1547-1552 ◽  
Author(s):  
M. Munakata ◽  
I. Huang ◽  
W. Mitzner ◽  
H. Menkes
Keyword(s):  
Guinea Pig ◽  
Protective Role ◽  
Airway Epithelial ◽  
Serosal Side ◽  
Epithelial Surface ◽  
Airway Responses ◽  
Airway Tone ◽  
Stimulation Of

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466–471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

scholarly journals Role of African swine fever virus (ASFV) proteins EP153R and EP402R in reducing viral persistence and virulence from attenuated BeninΔDP148R

2021 ◽  
Author(s):  
Vlad Petrovan ◽  
Anusyah Rathakrishnan ◽  
Muneeb Islam ◽  
Lynnette Goatley ◽  
Katy Moffat ◽  
...  
Keyword(s):  
Virus Replication ◽  
Vaccine Development ◽  
African Swine Fever Virus ◽  
Clinical Signs ◽  
African Swine Fever ◽  
Viral Persistence ◽  
Fever Virus ◽  
Post Immunization

The limited knowledge on the role of many of the approximately 170 proteins encoded by African swine fever virus restricts progress towards vaccine development. In this study we investigated the effect of deleting combinations of different genes from a previously attenuated virus, BeninΔDP148R on: virus replication in macrophages, virus persistence and clinical signs post immunization, and induction of protection against challenge. Deletion of either EP402R or EP153R genes individually or in combination from BeninΔDP148R did not reduce virus replication in vitro. However, deletion of EP402R dramatically reduced viral persistence in vivo, whilst maintaining high levels of protection against challenge. The additional deletion of EP153R (BeninΔDP148RΔEP153RΔEP402R) further attenuated the virus and no viremia or clinical signs were observed post immunization. This was associated with decreased protection and detection of moderate levels of challenge virus in blood. Interestingly, the deletion of EP153R alone from BeninΔDP148R did not result in further virus attenuation and a slight increase in virus genome copies in blood was observed at different times post immunization when compared with BeninΔDP148R. These results show that EP402R and EP153R have a synergistic role in promoting viremia, however EP153R alone does not seem to have a major impact on virus levels in blood.

The relationship between motor activity and transmural potential difference in the guinea pig intestine in vitro: is there a neural link?

1986 ◽  
Vol 64 (7) ◽  
pp. 993-998 ◽  
Author(s):  
Beverley Greenwood ◽  
Stephanie Diamant ◽  
J. S. Davison
Keyword(s):  
Guinea Pig ◽  
Motor Activity ◽  
Colonic Motility ◽  
Potential Difference ◽  
Histological Data ◽  
The Relationship ◽  
Spontaneous Fluctuations ◽  
Pig Jejunum

The aim of the experiments was to examine, in vitro, the role of the enteric nervous system in the relationship between motor activity and transmural potential difference (PD) in the guinea pig jejunum and colon using the nerve blocking agents tetrodotoxin (TTX) and aconitine. Histological data showed that perfusion of the intestinal segments with gassed Hepes solution was essential for the maintenance of transmural PD. Disruption of the mucosa was associated with a loss of spontaneous fluctuations in transmural PD without any loss of spontaneous motor activity. Under spontaneous conditions, a neural pathway exists linking jejunal and colonic motility with transmural PD. However, in some cases a mechanical link was also apparent, as an attenuated TTX and aconitine–resistant component.

scholarly journals Role of microRNAs as Clinical Cancer Biomarkers for Ovarian Cancer: A Short Overview

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 169 ◽  
Author(s):  
Cristina Elena Staicu ◽  
Dragoș-Valentin Predescu ◽  
Călin Mircea Rusu ◽  
Beatrice Mihaela Radu ◽  
Dragos Cretoiu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Simultaneous Detection ◽  
Clinical Signs ◽  
In Vivo Models ◽  
Circulating Micrornas ◽  
Clinical Biomarkers ◽  
Molecular Clustering

Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs are promising biomarkers in this respect. In this paper, we review the most recent advances regarding the alterations of microRNAs in ovarian cancer. We have briefly described the contribution of miRNAs in the mechanisms of ovarian cancer invasion, metastasis, and chemotherapy sensitivity. We have also summarized the alterations underwent by microRNAs in solid ovarian tumors, in animal models for ovarian cancer, and in various ovarian cancer cell lines as compared to previous reviews that were only focused the circulating microRNAs as biomarkers. In this context, we consider that the biomarker screening should not be limited to circulating microRNAs per se, but rather to the simultaneous detection of the same microRNA alteration in solid tumors, in order to understand the differences between the detection of nucleic acids in early vs. late stages of cancer. Moreover, in vitro and in vivo models should also validate these microRNAs, which could be very helpful as preclinical testing platforms for pharmacological and/or molecular genetic approaches targeting microRNAs. The enormous quantity of data produced by preclinical and clinical studies regarding the role of microRNAs that act synergistically in tumorigenesis mechanisms that are associated with ovarian cancer subtypes, should be gathered, integrated, and compared by adequate methods, including molecular clustering. In this respect, molecular clustering analysis should contribute to the discovery of best biomarkers-based microRNAs assays that will enable rapid, efficient, and cost-effective detection of ovarian cancer in early stages. In conclusion, identifying the appropriate microRNAs as clinical biomarkers in ovarian cancer might improve the life quality of patients.

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