The rabbit mesenteric vein: a specific bioassay for substance P

1978 ◽  
Vol 56 (4) ◽  
pp. 603-609 ◽  
Author(s):  
A. Bérubé ◽  
F. Marceau ◽  
J. N. Drouin ◽  
F. Rioux ◽  
D. Regoli
Keyword(s):  
Substance P ◽  
De Novo ◽  
Smooth Muscles ◽  
High Sensitivity ◽  
Mass Action ◽  
Response Curves ◽  
Mesenteric Vein ◽  
Mass Action Law ◽  
New Type ◽  
Specific Receptors

The anterior mesenteric vein of the rabbit responds to substance P with dose-dependent contractions and is among the vascular smooth muscles most sensitive to this peptide. In spite of its high sensitivity to numerous other agents, including angiotensin and bradykinin, the rabbit mesenteric vein can be made selective for substance P by the use of specific inhibitors that will prevent the myotropic effects of acetylcholine, catecholamines, histamine, 5-hydroxytryptamine, and of the two above-mentioned peptides, without modifying the contractions elicited by substance P. It appears that this peptide acts directly on specific receptors and not through the release of neurotransmitters. Interference by intramural prostaglandins is excluded because substance P is equally active on tissues pretreated with indomethacin or untreated.Dose–response curves obtained with substance P are close to the theoretical curves predicted by the mass action law. The rabbit mesenteric vein contains a new type of receptor for bradykinin, recently identified (REGOLI, D., MARCEAU, F., and BARABÉ, J. 1978. De novo formation of vascular receptors for bradykinin. Can. J. Physiol. Pharmacol. 56, in press.). The action of bradykinin on this receptor can be prevented with the use of specific and competitive inhibitors and, therefore, the mesenteric vein will distinguish between peptides of the kinins or of the substance P types.

Receptors for bradykinin in rabbit aortae

1977 ◽  
Vol 55 (4) ◽  
pp. 855-867 ◽  
Author(s):  
D. Regoli ◽  
J. Barabé ◽  
W. K. Park
Keyword(s):  
Dose Response ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Mass Action ◽  
Response Curves ◽  
Terminal Fragment ◽  
Mass Action Law ◽  
New Type ◽  
Specific Receptors ◽  
Stimulation Of

Rabbit aorta strips respond to bradykinin (BK) and to the C-terminal fragment of BK, the octapeptide 1-8 BK (Octa) with sustained contractions which are presumably due to the stimulation of specific receptors, because they remain unchanged in presence of phentolamine, methysergide, mepyramine, 8-Leu-ATII, and indomethacin. Experimental dose–response curves of BK and Octa are very similar to the theoretical curves predicted by the mass-action law and show the classical hyperbolic shape; ratios of doses producing 16% and 84% of maximum effects are 1:20 for Octa and 1:19 for BK. The relations of stimulus and effect are linear, suggesting that the extents of the contractions are proportional to the number of receptors occupied by the agonists.Structure–activity studies performed with fragments and analogues of BK and with analogues of Octa have shown that 8-Phe is essential for activation of the aortic receptor, and plays an important role for the affinity. The octapeptide 1-8 sequence is more favorable than the nonapeptide, because BK (pD2 = 6.40) is less potent than Octa (pD2 = 7.19) and 9-Ala BK is a partial agonist.Antagonists for both Octa and BK have been found by replacing 8-Phe with aliphatic residues (Ala, Nle, Leu, Leu-OMe) in the octapeptide. Affinities of 8-Leu-Octa (pA2 = 6.75) and 8-Leu-OMe-Octa (pA2 = 6.66) for the aortic receptors are fairly high and the antagonism appears to be of the competitive type because pA2 – pA10 is close to 0.95 for both compounds.The inhibitory effect of these two compounds are specific for Octa and BK. It is concluded that rabbit aortae contain a new type of receptor for BK, different from those found in the intestine and the uterus of several species.

Pharmacological studies of kinins in venous smooth muscles

1981 ◽  
Vol 59 (4) ◽  
pp. 371-379 ◽  
Author(s):  
P. Gaudreau ◽  
J. Barabé ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Guinea Pig ◽  
Jugular Vein ◽  
Biological Activities ◽  
Smooth Muscles ◽  
Response Curves ◽  
Kininase Ii ◽  
Structure Activity ◽  
Hexyl Ester ◽  
Pharmacological Studies ◽  
Specific Receptors

The myotropic effects of bradykinin (BK) and other kinins in two isolated veins, the rabbit jugular and the guinea pig anterior mesenteric, have been studied. The effects of degradation on the biological activities of these compounds and the receptor types mediating their myotropic effects have been determined.It has been found that contractions elicited by kinins in these veins result from direct actions on specific receptors. Both veins contain active kininase II (but not active carboxypeptidases A or B) which interferes with the measurement of the myotropic effects and can be blocked by 1-(D-3-mereapto-2-methyl-3-oxopropyl)-L-proline (SQ 14225). The slopes but not the maxima of the concentration–response curves of BK and other kinins measured in the presence of SQ 14225 are different from those recorded in its absence whereas no significant changes are observed in concentration–response curves obtained with the analogue [D-Phe8]-BK, which resists degradation by kininase II.BK is more potent than its fragment sequence des-Arg9-BK and the effects of kinins are antagonized by dihydrochlorprothixene and β-phenylalanine hexyl ester. These findings suggest that the rabbit jugular and the guinea pig anterior mesenteric veins contain receptors of the B2 type.The findings presented in this paper indicate that the rabbit jugular vein and the guinea pig anterior mesenteric vein are sensitive preparations for kinins and they can be useful for structure–activity studies of these peptides. A correct evaluation of the relative affinities of various kinins is, however, only possible by eliminating the interference of kininase II.

Application of Drug–Receptor Theories to Angiotensin

1973 ◽  
Vol 51 (9) ◽  
pp. 665-672 ◽  
Author(s):  
F. Rioux ◽  
W. K. Park ◽  
D. Regoli
Keyword(s):  
New York ◽  
Smooth Muscle ◽  
Rabbit Aorta ◽  
Biologically Active ◽  
Mass Action ◽  
Intrinsic Activity ◽  
Rat Stomach ◽  
Response Curves ◽  
Threshold Phenomenon ◽  
Specific Receptors

The myotropic action of angiotensin II has been studied on two smooth muscle preparations: the strip of rat stomach and of rabbit thoracic aorta. Contractions evoked by angiotensin are not modified by atropine, methysergide, and diphenhydramine on the rat stomach or by phentolamine, methysergide, and diphenhydramine on the rabbit aorta. It appears that angiotensin acts directly on specific receptors and not through release of acetylcholine on the stomach or of noradrenaline on the aorta. Interference by intramural prostaglandins is excluded because angiotensin is equally active on tissues pretreated or not with indomethacin.Dose–response curves obtained with angiotensin on the two tissues are close to the theoretical curves predicted by the mass–action law. The relations stimulus effect is linear, indicating that the extent of the contraction is proportional to the number of receptors occupied by the agonist. No threshold phenomenon or spare receptor capacity could be demonstrated in either tissue. It is therefore concluded that the interaction of angiotensin with its specific receptors in the two smooth muscle preparations can be analyzed quantitatively with the occupation theory by applying the concepts of affinity and intrinsic activity as defined by Ariens in 1964. (Molecular pharmacology. Vol. 1. The mode of action of biologically active compounds. Academic Press, New York.)

Development of imaging plate for a TEM and its characteristics

1989 ◽  
Vol 47 ◽  
pp. 100-101
Author(s):  
N. Mori ◽  
T. Oikawa ◽  
Y. Harada ◽  
J. Miyahara ◽  
T. Matsuo
Keyword(s):  
Dynamic Range ◽  
Protective Layer ◽  
High Sensitivity ◽  
Imaging Plate ◽  
Phosphor Layer ◽  
Imaging Device ◽  
X Ray Imaging ◽  
New Type ◽  
Basic Characteristics ◽  
Reading System

The Imaging Plate (IP) is a new type imaging device, which was developed for diagnostic x ray imaging. We have reported that usage of the IP for a TEM has many merits; those are high sensitivity, wide dynamic range, and good linearity. However in the previous report the reading system was prototype drum-type-scanner, and IP was also experimentally made, which phosphor layer was 50μm thick with no protective layer. So special care was needed to handle them, and they were used only to make sure the basic characteristics. In this article we report the result of newly developed reading, printing system and high resolution IP for practical use. We mainly discuss the characteristics of the IP here. (Precise performance concerned with the reader and other system are reported in the other article.)Fig.1 shows the schematic cross section of the IP. The IP consists of three parts; protective layer, phosphor layer and support.

Studies on Activator Formation in Human Plasma with Streptokinase

1973 ◽  
Vol 30 (02) ◽  
pp. 381-392
Author(s):  
M Martin ◽  
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Mass Action ◽  
Activator Concentration ◽  
Kinetic Effect ◽  
Mass Action Law

SummaryThe plasminogen-streptokinase complex called “activator” was present in diluted plasma in the form of a largely dissociated mixture. More than ⅞ of the streptokinase and plasminogen molecules were available for further activator formation.The activator is probably a dissociated complex of the formulaStreptokinase + Plasminogen ⇄ Activator.The fact that an increase in activator concentration by x times is obtained by multiplying either the streptokinase content by the factor y or the plasminogen concentration by the same factor y would point to a kinetic effect along the lines of the mass action law.

scholarly journals Ag nanoparticles outperform Au nanoparticles for the use as label in electrochemical point-of-care sensors

2021 ◽  
Author(s):  
Franziska Beck ◽  
Carina Horn ◽  
Antje J. Baeumner
Keyword(s):  
Limit Of Detection ◽  
Point Of Care ◽  
Automatic Measurement ◽  
High Sensitivity ◽  
Differential Pulse ◽  
Small Sample ◽  
Blood Protein ◽  
User Friendliness ◽  
Response Curves ◽  
Assay Protocol

AbstractElectrochemical immunosensors enable rapid analyte quantification in small sample volumes, and have been demonstrated to provide high sensitivity and selectivity, simple miniaturization, and easy sensor production strategies. As a point-of-care (POC) format, user-friendliness is equally important and most often not combinable with high sensitivity. As such, we demonstrate here that a sequence of metal oxidation and reduction, followed by stripping via differential pulse voltammetry (DPV), provides lowest limits of detection within a 2-min automatic measurement. In exchanging gold nanoparticles (AuNPs), which dominate in the development of POC sensors, with silver nanoparticles (AgNPs), not only better sensitivity was obtained, but more importantly, the assay protocol could be simplified to match POC requirements. Specifically, we studied both nanoparticles as reporter labels in a sandwich immunoassay with the blood protein biomarker NT-proBNP. For both kinds of nanoparticles, the dose-response curves easily covered the ng∙mL−1 range. The mean standard deviation of all measurements of 17% (n ≥ 4) and a limit of detection of 26 ng∙mL−1 were achieved using AuNPs, but their detection requires addition of HCl, which is impossible in a POC format. In contrast, since AgNPs are electrochemically less stable, they enabled a simplified assay protocol and provided even lower LODs of 4.0 ng∙mL−1 in buffer and 4.7 ng∙mL−1 in human serum while maintaining the same or even better assay reliability, storage stability, and easy antibody immobilization protocols. Thus, in direct comparison, AgNPs clearly outperform AuNPs in desirable POC electrochemical assays and should gain much more attention in the future development of such biosensors.

scholarly journals Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Rose Brannon ◽  
Gowtham Jayakumaran ◽  
Monica Diosdado ◽  
Juber Patel ◽  
Anna Razumova ◽  
...  
Keyword(s):  
Cancer Patients ◽  
De Novo ◽  
Low Frequency ◽  
High Sensitivity ◽  
Clinical Analysis ◽  
De Novo Mutation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Somatic Alterations ◽  
Mutation Profiling

AbstractCirculating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.

The Interferons

1984 ◽  
Vol 92 (3) ◽  
pp. 365-368 ◽  
Author(s):  
William J. Richtsmeier
Keyword(s):  
Nucleic Acid ◽  
Antineoplastic Agents ◽  
De Novo ◽  
Synthetic Activity ◽  
Antiviral Resistance ◽  
Virus Propagation ◽  
The Public ◽  
Interferon Inducers ◽  
Basic Criterion ◽  
Specific Receptors

The interferons (IFNs) are a group of proteins produced by cells of all vertebrate animals in response to a variety of stimuli. The ability to stimulate antiviral resistance, which was the first observed property of the IFNs, is still of great interest and remains the basic criterion by which the interferons are measured 1 (even into the most recent era of radioimmunoassay systems). It is the recent clinical uses of these substances as antineoplastic agents that has brought them to the attention of clinicians and the public in general. The IFN molecules exert their effects, much as hormones do, by attaching to specific receptors on other cells of the same species. Once attached, the IFNs induce cells to undergo a series of biochemical changes that renders them resistant to further virus propagation. To be an IFN, a substance must be a protein devoid of accompanying nucleic acid or endotoxin (both of which are interferon inducers). Treated cells must undergo de novo RNA and protein synthetic activity to acquire antiviral resistance.

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