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.

scholarly journals Effect of adrenomedullin infusion on basal and stimulated aldosterone secretion in conscious sheep with cervical adrenal autotransplants

2000 ◽  
Vol 166 (2) ◽  
pp. 389-399 ◽  
Author(s):  
R Salemi ◽  
JG McDougall ◽  
KJ Hardy ◽  
EM Wintour
Keyword(s):  
Adrenal Gland ◽  
Zona Glomerulosa ◽  
Cortisol Secretion ◽  
Aldosterone Secretion ◽  
Stimulation Experiments ◽  
Gland Function ◽  
Conscious Sheep ◽  
Stimulation Of

In vivo and in vitro studies have shown conflicting effects of adrenomedullin (ADM) on the secretion of steroid hormones from the adrenal gland. While some investigators report no effect of this peptide on the output of various hormones, others have reported both stimulatory and inhibitory roles for ADM. We have shown that basal aldosterone secretion rate (ASR), in conscious sheep with cervical adrenal autotransplants, did not change when ADM was infused directly into the adrenal arterial supply. While not affecting basal ASR, ADM did produce pronounced increases in adrenal blood flow (BF). This elevation of BF in association with ADM infusion was seen in all subsequent experiments. When aldosterone output was acutely stimulated by angiotensin II (AngII), potassium chloride (KCl) and adrenocorticotrophic hormone (ACTH), ADM was seen to drastically reduce the secretion of aldosterone with all agonists studied. After pre-exposure to ADM, all three agonists increased ASR but the magnitude of the responses were somewhat blunted. ADM did not have the same effect on cortisol secretion stimulated by ACTH, suggesting that the ability of this peptide to influence adrenal gland function is limited to the zona glomerulosa. In conditions of chronic elevation of aldosterone levels, such as in Na deficiency, ADM did not display the same inhibitory abilities seen in the acute stimulation experiments. Hence, ADM has been shown to have a direct, inhibitory role on the acute stimulation of aldosterone by AngII, KCl and ACTH while not affecting basal or chronic aldosterone secretion or cortisol secretion stimulated by ACTH.

2-Chloroadenosine increases calcium mobilization from mouse calvaria in vitro

1982 ◽  
Vol 100 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Ulf Lerner ◽  
Bertil B. Fredholm
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Bone Tissue ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Amp Accumulation ◽  
Adenosine Analogue ◽  
Stimulation Of

Abstract. The effect of 2-chloroadenosine on bone resorption and on cyclic AMP formation in murine calvarial bones in vitro was investigated. 2-Chloroadenosine increased the release of 45Ca from the cultured bones, but had no effect on dead bones, indicating that the effect is cell mediated. The adenosine analogue remained in the medium for 48 h and caused a transient stimulation of the formation of cyclic AMP. The dose-response curve for the stimulatory effect on cyclic AMP accumulation was linear up to 10−4m. The dose-response curve for 45Ca release was linear from 3 × 10−7 m to 3 × 10−5 m but then showed a decline in the response. 8-Bromo cyclic AMP inhibited the release of 45Ca in 24 h cultures. The initial stimulatory effect on bone resorption by 2-chloroadenosine may therefore not depend on cyclic AMP. The level of inosine increased during culture indicating that adenosine is formed by bone tissue.

Formation of releasable γ-aminobutyrate from putrescine by rat adrenal slices in vitro

1989 ◽  
Vol 123 (2) ◽  
pp. 227-232 ◽  
Author(s):  
B. B. Oon ◽  
P. R. Scraggs ◽  
B. Gillham
Keyword(s):  
Catalytic Activity ◽  
Adrenal Gland ◽  
Incubation Medium ◽  
Functional Significance ◽  
Response Curve ◽  
Diamine Oxidase ◽  
Adrenal Glands ◽  
Metabolic Transformation ◽  
Stimulation Of

ABSTRACT Rat adrenal gland slices, when incubated in vitro with [1,4-14C]putrescine, accumulate the radioactive diamine and convert it, in part, to a compound indistinguishable (in four separative systems) from [14C]γ-aminobutyrate (GABA). Adrenal glands taken from animals that had undergone adrenal enucleation 28 days previously, so that the cortex of the tissue had regenerated, likewise formed [14C]GABA from [1,4-14C]putrescine. Putrescine-derived GABA was released from adrenal slices in vitro by 48 mmol K+/l, the release being dependent upon the presence of Ca2+ in the incubation medium. ACTH(1–24) and 8-bromocyclic AMP both provoked a dose-related release of putrescine-derived GABA, although the dose–response curve for the latter differed somewhat from that for the release of corticosterone by this secretogogue. The enzyme believed to be responsible for the first step in the metabolic transformation of putrescine into GABA, diamine oxidase (DAO), is present in extracts of adrenal tissue and its catalytic activity underwent a transient increase followed by a fall below resting levels upon stimulation of adrenal slices with ACTH(1–24). The conclusion that this enzyme initiates the formation of GABA by this pathway is indicated by the observation that adrenal slices pretreated with the DAO inhibitor, aminoguanidine, released significantly less [1,4-14C]putrescine-derived GABA in response to 48 mmol K+/l than did control tissues. The functional significance of these findings remains to be established. Journal of Endocrinology (1989) 123, 227–232

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.

Enhanced coupling of adenylate cyclase to lipolysis in permeabilized adipocytes from trained rats

1991 ◽  
Vol 71 (1) ◽  
pp. 23-29 ◽  
Author(s):  
T. Izawa ◽  
T. Komabayashi ◽  
T. Mochizuki ◽  
K. Suda ◽  
M. Tsuboi
Keyword(s):  
Adenylate Cyclase ◽  
Dose Response ◽  
Response Curve ◽  
Positive Relationship ◽  
Regression Coefficient ◽  
Permeabilized Cells ◽  
Major Mechanism ◽  
The Difference ◽  
And Control ◽  
Stimulation Of

Digitonin-permeabilized adipocytes were used to study the coupling of adenylate cyclase (AC) to lipolysis in exercise-trained rats. Isoproterenol-(IPR) stimulated lipolysis in permeabilized cells was significantly greater in trained than in control rats. Under essentially identical conditions, the dose-response curve for IPR stimulation of AC activity in the absence of 3-isobutyl-1-methylxanthine was similar in trained and control rats. However, the potency of stimulation by IPR as a percentage of the basal level was greater in trained rats. AC activity and lipolysis in the presence of 3-isobutyl-1-methylxanthine were also significantly greater in trained than in control rats. Least-squares analysis by plotting the log AC vs. lipolysis values showed that the regression coefficient was about three-fold greater in trained than in control rats. The concentration of endogenous adenosine 3′,5′-cyclic monophosphate (cAMP) needed to produce a half-maximal lipolytic response was 18.58 and 10.81 pmol.min-1.10(6) cells-1 in control and trained rats, respectively. Thus a positive relationship existed between lipolysis and AC activity, with a tighter coupling in trained rats. Lipolysis in response to exogenous cAMP tended to be greater in trained than in control rats, and the difference was statistically significant for 50 microM and 10 mM cAMP. Our finding support the concept that the major mechanism of enhanced lipolysis in trained rats was an increase in the activity of enzymatic step(s) distal to cAMP.

THE IN VITRO ACTION OF ACTH ON THE OXYGEN CONSUMPTION OF SLICES OF CATTLE ADRENAL CORTEX

1953 ◽  
Vol 9 (4) ◽  
pp. 379-390 ◽  
Author(s):  
M. REISS ◽  
EVA BRUMMEL ◽  
I. D. K. HALKERSTON ◽  
F. E. BADRICK ◽  
M. FENWICK
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Linear Relationship ◽  
Adrenal Cortex ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Biological Assay ◽  
Percentage Increase ◽  
Small Doses

A technique for measuring the action of small doses of ACTH on the oxygen consumption of slices of cattle adrenal cortex is described. The oxygen consumption rate of such slices in vitro is increased by ACTH. A linear relationship between logarithm of the dose of ACTH and the percentage increase in the rate of oxygen uptake is obtained with this method, and its suitability for biological assay purposes has been investigated. The question of the specificity of this action of ACTH is discussed.

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.

Effects of inhibitors of cyclic nucleotide phosphodiesterase on actions of cholecystokinin, bombesin, and carbachol on pancreatic acini

1983 ◽  
Vol 245 (5) ◽  
pp. G676-G680
Author(s):  
J. D. Gardner ◽  
V. E. Sutliff ◽  
M. D. Walker ◽  
R. T. Jensen
Keyword(s):  
Dose Response ◽  
Cyclic Nucleotide ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Rightward Shift ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas two inhibitors of cyclic nucleotide phosphodiesterase, Ro 20-1724 and 3-isobutyl-1-methylxanthine (IBMX), augmented the increase in amylase secretion caused by supramaximal concentrations of cholecystokinin but did not alter the stimulation of enzyme secretion caused by bombesin. The augmentations of the action of cholecystokinin caused by Ro 20-1724 or IBMX could be reproduced by 8-bromo-cAMP. When tested alone or with theophylline, cholecystokinin did not alter cAMP in pancreatic acini; however, with Ro 20-1724 or IBMX, concentrations of cholecystokinin that were supramaximal for stimulating amylase secretion caused a significant increase in cellular cAMP. These findings indicate that Ro 20-1724 and IBMX augment the action of cholecystokinin on enzyme secretion by inhibiting cyclic nucleotide phosphodiesterase and allowing a significant cholecystokinin-induced increase in cellular cAMP. IBMX but not Ro 20-1724 caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion caused by carbachol. IBMX also caused a parallel rightward shift in the dose-response curve for the stimulation of outflux of 45Ca caused by carbachol. These results indicate that IBMX, but not Ro 20-1724, can function as a muscarinic cholinergic antagonist.

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.

IN VITRO AND IN VIVO EFFECT OF GROWTH HORMONE ON ALDOSTERONE SECRETION

1960 ◽  
Vol 38 (1) ◽  
pp. 1069-1075
Author(s):  
O. J. Lucis ◽  
E. H. Venning
Keyword(s):  
Growth Hormone ◽  
Adrenal Gland ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Hypophysectomized Rats

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.

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