The Effect of Temperature Changes on Tachyphylaxis to Angiotensin In Vitro

1972 ◽  
Vol 50 (6) ◽  
pp. 498-502 ◽  
Author(s):  
Patrick LeMorvan ◽  
Djuro Palaic
Keyword(s):  
Cell Membrane ◽  
Guinea Pig ◽  
Dose Response ◽  
Binding Sites ◽  
Response Curve ◽  
Effect Of Temperature ◽  
Maximal Response ◽  
Nonspecific Binding ◽  
Temperature Changes

The effect of heat on the contractility and binding of 14C-angiotensin to guinea pig aortic strips was studied. It was found that heating strips to 47 °C for 20 min causes an increase in maximal response as well as a shift to the left of the dose–response curve for angiotensin while responses to noradrenaline (NA) remain unchanged. This procedure also increases the onset of tachyphylaxis to 10−5 M angiotensin. Heating (47 °C) for varying periods of time decreases the binding of 14C-angiotensin by about 60%. This effect does not seem to be related to the time of heating. It is postulated that this reduction in binding reflects denaturation of nonspecific binding sites on the cell membrane. Heating (47 °C, 20 min) enhanced the binding of 14C-angiotensin to aortic strips which had been rendered tachyphylactic to 10−5 M angiotensin. It is suggested that this is due to the induction of new binding sites.

Interaction of enkephalin and caerulein on guinea pig small intestine

1983 ◽  
Vol 244 (1) ◽  
pp. G65-G70
Author(s):  
W. M. Yau ◽  
P. F. Lingle ◽  
M. L. Youther
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Dose Response ◽  
Response Curve ◽  
Acetylcholine Release ◽  
Control Level ◽  
Release Studies ◽  
Release Of Acetylcholine

This is a report on the effect of caerulein and methionine-enkephalin interaction on mechanical contraction and acetylcholine release in vitro. The ability of enkephalin to relax caerulein-induced contractions and the manner in which the caerulein dose-response curve was shifted in the presence of enkephalin strongly suggest that enkephalin and caerulein are functional antagonists in this system. The failure of enkephalin to alter the action of exogenous acetylcholine implies that such an antagonism is not mediated through a competition with postsynaptic muscarinic receptors on the muscle. Data from acetylcholine-release studies indicate that caerulein stimulation was dose related. As with the mechanical contractions, the release of acetylcholine in response to caerulein was inhibited by enkephalin. However, naloxone was capable of blocking this inhibition and restoring the release to its control level without interfering with caerulein stimulation. These data provide evidence for the modulatory roles of neuronal peptides in the cholinergic control of gut motility.

Cholinergic responsiveness of respiratory and vascular tissues in two different rat strains

1988 ◽  
Vol 64 (1) ◽  
pp. 323-328 ◽  
Author(s):  
M. Badier ◽  
M. Soler ◽  
M. Mallea ◽  
S. Delpierre ◽  
J. Orehek
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Maximal Response ◽  
Arterial Smooth Muscle ◽  
Cholinergic Agents

The airway and systemic arterial smooth muscle responsiveness to cholinergic agents of two strains of rats, Rat Albino (RA) and Brown Norway (BN), was compared in vivo and in vitro. In vivo, we measured the doses of carbachol that induced a 100% increase in lung resistance (PD100 RL), a 50% decrease in dynamic lung compliance (PD50 Cdyn), and the value of systolic blood pressure at the carbachol dose of 10 micrograms (Pa 10 micrograms). In vitro airway smooth muscle and systemic arterial smooth muscle responsiveness was assessed by measuring the maximal response to acetylcholine, the slope of the linear portion of the dose-response curve, and the negative logarithm of the molar concentration of acetylcholine producing 50% of the maximal response (pD2). PD100 and PD50 were about four times greater in BN rats than in RA rats. In contrast, Pa 10 micrograms was 1.5 lower in the BN rats. These differences persisted after bivagotomy. Tracheal pD2 was 25% greater in the RA than in the BN strain. The mean dose-response curve of parenchymal strips of RA rats was situated upward and to the left of the BN curve, but the reverse was observed for aortic smooth muscle dose-response curves. Thus 1) airway smooth muscle responsiveness to cholinergic agents is greater in RA strain than in BN, but the reverse is true for systemic arterial smooth muscle responsiveness; and 2) these differences are not due to factors extrinsic to the smooth muscle, since they occurred in vitro and may depend on different densities of muscarinic receptors.

Interaction between gastrin, CCK, and secretin on canine antral smooth muscle in vitro.

1979 ◽  
Vol 236 (1) ◽  
pp. E39
Author(s):  
J W Fara ◽  
M Praissman ◽  
J M Berkowitz
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Receptor Site ◽  
Isometric Tension ◽  
Dose Response Curve ◽  
Maximal Response

This study compared the actions and interactions of human synthetic gastrin, octapeptide-cholecystokinin (OP-CCK), cholecystokinin (CCK), and secretin on the amplitude of isometric tension developed in strips of dog antral smooth muscle in vitro. Cholecystokinin, OP-CCK, and gastrin produced maximal stimulatory effects at 7.5 x 10(-9), 4.5 x 10(-9), and 3.5 x 10(-9) M, respectively. Secretin alone was ineffective up to 2.5 x 10(-8) M. Observed maximal responses to gastrin, OP-CCK, and CCK tested alone were not significantly different. A submaximal gastrin dose added with OP-CCK, shifted the OP-CCK dose-response curve to the left and significantly reduced the D50, but the calculated maximal response (CMR) did not change. Also, submaximal OP-CCK plus gastrin shifted the gastrin dose-response curve to the left and significantly lowered the D50 with no change in CMR. Secretin decreased CMR but did not change the D50 for gastrin. Responses obtained to gastrin and OP-CCK tested alone were not affected by tetrodotoxin (1 x 10(-5) M), hexamethonium bromide (4 x 10(-5) M), or atropine (1 x 10(-7) M). Larger doses of atropine (5 x 10(-6) M) reduced peptide responses an average 30%. The results indicate that OP-CCK, CCK, and gastrin share a common noncholinergic receptor site. Secretin acts at a different receptor site.

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

EFFECT OF VARIOUS PREPARATIONS OF PITUITARY AND DIENCEPHALON ON THE IN VITRO SECRETION OF ALDOSTERONE AND CORTICOSTERONE BY THE RAT ADRENAL GLAND

1961 ◽  
Vol 39 (5) ◽  
pp. 901-913 ◽  
Author(s):  
O. J. Lucis ◽  
I. Dyrenfurth ◽  
E. H. Venning
Keyword(s):  
Adrenal Gland ◽  
Linear Relationship ◽  
Dose Response ◽  
Response Curve ◽  
Maximum Effect ◽  
Percentage Increase ◽  
Aldosterone Secretion ◽  
Maximal Stimulation ◽  
Stimulation Of

Purified corticotropin and ACTH peptides increased the secretion of aldosterone, corticosterone, and an unidentified compound RT4in incubated rat adrenal tissue. When the response was expressed as a percentage increase above that of the control tissue, the increases in corticosterone and compound RT4followed a sigmoid log dose – response curve. The maximum effect on aldosterone was obtained at a time when the response curve for corticosterone assumed a linear relationship between the response and the logarithm of the dose of ACTH. This dose level was considerably less than that required for maximal stimulation of corticosterone.The capacity of the ACTH peptides α1+α2and δ′ for stimulating aldosterone secretion could be greatly diminished by allowing solutions of these fractions to stand at 5 °C for 1 week. These solutions still retained their ability to stimulate corticosterone secretion.Saline suspensions and extracts of fresh hog diencephalon contained a factor which selectively stimulated aldosterone secretion.

Mechanisms of histamine-induced contraction of canine airway smooth muscle

1983 ◽  
Vol 55 (1) ◽  
pp. 22-26 ◽  
Author(s):  
S. Shore ◽  
C. G. Irvin ◽  
T. Shenkier ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Line Tension ◽  
Isometric Tension ◽  
Dose Response Curve ◽  
Base Line ◽  
Histamine Concentration ◽  
Release Of Acetylcholine

We studied the effects of atropine (10(-10) to 10(-6) M), tetrodotoxin (TTX) (10(-6) g/ml), and neostigmine (10(-7) M) on the histamine dose-response curve of canine tracheal smooth muscle (TSM) in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples, whereas neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10(-6), 10(-8), and 10(-10) M atropine, Tmax was 57, 74, and 88%, respectively, of its value in paired control samples. Atropine, 10(-9) to 10(-6) M, increased the concentration of histamine which produced 20% of Tmax, whereas 10(-6) M also increased the concentration required to produce 50% of Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P less than 0.05). Our data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine either accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.

Alterations in the functional properties of skinned fibers from denervated rabbit skeletal muscle

1990 ◽  
Vol 259 (3) ◽  
pp. C503-C506 ◽  
Author(s):  
M. M. Trachez ◽  
R. T. Sudo ◽  
G. Suarez-Kurtz
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Functional Properties ◽  
Dose Response ◽  
Response Curve ◽  
Extensor Digitorum Longus ◽  
Isometric Tension ◽  
Skinned Fibers ◽  
Spontaneous Release

Isometric tension was recorded in vitro from chemically skinned fibers obtained from normal and 14-day-denervated extensor digitorum longus muscles of the rabbit. Denervation potentiated the tensions elicited by pCa 6.0 but did not modify the pCa value (5.6) required for maximum tension. Ca2+ transport across the membranes of the sarcoplasmic reticulum (SR) was markedly affected by denervation. Thus the rate of ATP-dependent net Ca2+ uptake increased significantly, and the spontaneous release ("leakage") of the Ca2+ stored in the SR was significantly reduced in denervated fibers. These effects lead to increased accumulation of Ca2+ in the lumen of the SR. The dose-response curve for the halothane-induced contractures of Ca2(+)-loaded skinned fibers was displaced to the left after denervation. Thus 0.7 mM halothane, a concentration that elicited no tension in 10 control fibers, induced contractures in the 10 denervated fibers tested. The potentiation of the halothane-induced tensions is attributed mainly to the larger stores of Ca2+ in the SR of denervated fibers. The possibility that denervation may also affect the interaction of halothane with the SR membranes is discussed.

scholarly journals Cd2 Sets Quantitative Thresholds in T Cell Activation

1999 ◽  
Vol 190 (10) ◽  
pp. 1383-1392 ◽  
Author(s):  
Martin F. Bachmann ◽  
Marijke Barner ◽  
Manfred Kopf
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Dose Response ◽  
Response Curve ◽  
Cell Activation ◽  
Dose Response Curve ◽  
Lymphocyte Function

It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell–antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose–response curve in vitro by a factor of 3–10. In comparison, stimulation of T cells in the absence of lymphocyte function–associated antigen (LFA)-1–intercellular adhesion molecule (ICAM)-1 interaction shifted the dose–response curve by a factor of 10, whereas absence of both CD2–CD48 and LFA-1–ICAM-1 interactions shifted the response by a factor of ∼100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca2+ fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

Bradykinin receptors localized by quantitative autoradiography in kidney, ureter, and bladder

1989 ◽  
Vol 256 (5) ◽  
pp. F909-F915 ◽  
Author(s):  
D. C. Manning ◽  
S. H. Snyder
Keyword(s):  
Guinea Pig ◽  
Binding Sites ◽  
Basal Membrane ◽  
Epithelial Layer ◽  
Bradykinin Receptors ◽  
High Affinity ◽  
Collecting Tubule ◽  
Tubule Cells

We have localized high affinity [3H]bradykinin receptor binding sites by in vitro autoradiography in kidney, ureter, and bladder of the guinea pig. The peptide pharmacology of the binding sites corresponds to that of high affinity physiological bradykinin receptors previously described (Manning, D. C., R. Vavrek, J. M. Stewart, and S. H. Snyder. J. Pharmacol. Exp. Ther. 237:504-512, 1986). In the kidney, receptors are concentrated in the medulla with negligible binding in the cortex. Medullary receptors are localized to the interstitium just beneath the basal membrane of collecting tubule cells and between tubules. In the ureter and bladder, receptors are confined to the lamina propria just beneath the epithelial layer. Localizations in the kidney may relate to the diuretic and natriuretic actions of bradykinin. Ureteral and bladder receptors may be associated with a role of bradykinin in pain and inflammation.

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