Relationship among sensitivity to adrenaline, plasma corticosterone level; and estrous cycle in rats

1995 ◽  
Vol 73 (5) ◽  
pp. 602-607 ◽  
Author(s):  
M. L. V. Rodrigues ◽  
F. K. Marcondes ◽  
R. C. Spadari-Bratfisch
Keyword(s):  
Estrous Cycle ◽  
Dose Response ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Extraneuronal Uptake ◽  
Response Curves ◽  
Experimental Conditions ◽  
Dose Response Curves ◽  
Right Atria

The dose–response curves to the chronotropic effect of adrenaline obtained in right atria isolated from female rats indicated an order of increasing sensitivity to adrenaline, at the pD2 level, according to the estrous cycle, as follows: estrus ≤ metestrus ≤ diestrus ≤ proestrus. Inhibition of neuronal and extraneuronal uptake shifted the dose–response curves to adrenaline to the left only in right atria isolated from rats during estrus or metestrus. Moreover, under these experimental conditions, right atria were subsensitive to adrenaline during proestrus, in contrast to metestrus. Plasma corticosterone levels were lower during estrus and higher at proestrus. There was a positive correlation between right atria sensitivity to adrenaline and plasma corticosterone levels and estrous cycle phases. Our results also suggest that in the rat right atria during proestrus, as opposed to the other phases of the estrous cycle, there was an endogenous inhibition of extraneuronal uptake together with some alteration at the adrenoceptor level and (or) at intracellular mechanisms beyond receptors.Key words: adrenergic response, female, adrenaline, chronotropism, right atria.

scholarly journals Modification of vasodilator response in streptozotocin-induced diabetic rat

1999 ◽  
Vol 77 (12) ◽  
pp. 980-985 ◽  
Author(s):  
Jean-François Bouchard ◽  
Éric C Dumont ◽  
Daniel Lamontagne
Keyword(s):  
Diabetes Mellitus ◽  
Adenylyl Cyclase ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Response Curves ◽  
Experimental Conditions ◽  
Isolated Hearts ◽  
Dose Response Curves

Functional dilatory response in streptozotocin-induced diabetic rats was investigated using thoracic aortas, isolated hearts, and mesenteric beds. Dose-response curves to the PGI2 analogue iloprost on phenylephrine-preconstricted rings of diabetic rats and controls were comparable. In contrast, decreased vasodilation in diabetic rats was observed when dose-response curves to iloprost were performed in hearts and on phenylephrine-preconstricted mesenteric beds. Dose-response curves to forskolin, an adenylyl cyclase activator, performed with hearts and phenylephrine-preconstricted aortic rings and isolated mesenteric beds of diabetic rats and controls were comparable. However, a decreased vasodilation to the ATP-sensitive potassium channel (KATP) activator lemakalim was observed in diabetic hearts, but not in aortic rings and mesenteric beds. In conclusion, under our experimental conditions, diabetes mellitus affects the vasodilation to iloprost in both coronary and mesenteric beds, but not in the aorta. In the heart, this modification of vascular reactivity may be due to a decrease in KATP channel mediated response and not to a decreased activity of adenylyl cyclase. At this time, in the isolated mesenteric bed, the mechanism of this modification in vascular reactivity remains unknown.Key words: diabetes mellitus, iloprost, KATP channels, adenylyl cyclase, aorta, coronary circulation, mesenteric bed.

Pharmacological evidence for β2-adrenoceptor in right atria from stressed female rats

1999 ◽  
Vol 77 (6) ◽  
pp. 432-440 ◽  
Author(s):  
R C Spadari-Bratfisch ◽  
I N Santos ◽  
LCM Vanderlei ◽  
F K Marcondes
Keyword(s):  
Estrous Cycle ◽  
Model Equation ◽  
Female Rats ◽  
Cycle Phase ◽  
Response Curves ◽  
Chronotropic Response ◽  
Site Model ◽  
Stressed Female ◽  
Right Atria ◽  
Shock Stress

The purpose of the present study was to demonstrate a physiological response to TA2005, a potent β2-adrenoceptor (β2-AR) selective agonist, in right atria isolated from stressed female rats under the influence of the estrous cycle. We obtained concentration-response curves to the agonist in the presence and in the absence of selective antagonists in right atria isolated from female rats submitted to three daily foot-shock sessions (30 min duration, 120 pulses of 1.0 mA, 1.0 s, applied at random intervals of 5-25 s) and sacrificed at estrus or diestrus. Our results showed that the pD2 values of TA2005 were not influenced by estrous cycle phase or foot-shock stress. However, in right atria from stressed rats sacrificed during diestrus, the concentration-response curve to TA2005 was biphasic, with a response being obtained at concentrations of 0.1 nM, whereas during estrus no response was observed at doses lower than 3 nM. ICI118,551, a β2-AR antagonist, abolished the response to nanomolar concentrations of TA2005 in right atria from stressed rats at diestrus, with no changes in agonist pD2 values in right atria from control rats (7.47 ± 0.09, p > 0.05) but a 3-fold decrease in pD2 values of TA2005 in right atria from foot shock stressed rats (7.90 ± 0.07, p [Formula: see text] 0.05). Concentration-response curves to TA2005 in the presence of ICI118,551 were best fitted by a one-site model equation. The β1-AR antagonist, CGP20712A, shifted to the right only the second part of the concentration-response curves to the agonist, unmasking the putative β2-AR-mediated response to the agonist in tissues isolated from stressed rats at diestrus. Under this condition, concentration-response curves to the agonist were best fitted by a two-site model equation. pD2 and maximum response of TA2005 interaction with β1- and putative β2-adrenoceptor components were calculated. Schild analyses gave a pKB value for CGP20712A that was typical for the interaction with β1-AR in each experimental group. pKB values for ICI118,551 could not be obtained in stressed rats sacrificed at diestrus since Schild plot slopes were lower than 1.0. In right atria from control rats, ICI118,551 pKB values were similar to reported values for the interaction of the antagonist with β1-AR. These results confirm that a heterogenous β-AR population mediating the chronotropic response to catecholamines can be demonstrated in right atria from foot shock stressed female rats sacrificed at diestrus. The stress-induced response seems to be mediated by the β2-AR subtype. Right atria from rats sacrificed during estrus are protected against stress-induced alterations on the homogeneity of β-AR population.Key words: foot-shock stress, TA2005, ICI118,551, CGP20712A, estrus, diestrus.

scholarly journals A Rapid, Sensitive and Reliable Assay for Inhibin Bioactivity

1987 ◽  
Vol 40 (1) ◽  
pp. 105 ◽  
Author(s):  
V WK Lee ◽  
Noelene Colvin ◽  
Helen Quigg ◽  
Lynne Atley ◽  
Julie McMaster ◽  
...  
Keyword(s):  
Dose Response ◽  
Culture Media ◽  
Rete Testis ◽  
Female Rats ◽  
Pituitary Cells ◽  
Response Curves ◽  
Cell Content ◽  
Practical Capacity ◽  
Pituitary Glands ◽  
Dose Response Curves

A rapid 2-day quantitative assay for inhibin bioactivity based on FSH secretion from pituitary cells of immature female rats is described. The bioassay exhibited steeper slopes, improved precision and greater (fourfold) sensitivity compared with a previously established pituitary FSH cell content assay. Whole pituitary glands were used for the preparation of pituitary cells and the method for cell dispersion required a single enzymatic treatment with trypsin. Cells (180000 viable cells per well) were dispensed into culture media containing inhibin and incubated for 48 h. Media were removed and assayed for FSH by radioimmunoassay. Using a ram rete testis fluid preparation as standard the inhibin dose-response curves of 25 consecutive experiments showed indices of precision of - O� 08(mean)[range - 0�04 to - 0�17] and Finney's G values of 0�017[0�003-0�06]. The mean ED40 was 0�17 units of in hi bin activity per well with interassay variation of 16�2% at this point of the dose-response curve. The assay had a practical capacity of 400 wells, permitting the measurement of dose-response curves of at least 40 unknowns with three dose points and triplicate wells per dose. The assay is specific for inhibin-containing preparations from several animal species. Overall, the assay is simple, precise, and sensitive, indicative of its applicability to the measurement of inhibin samples with low inhibin bioactivity and to the screening of large numbers of fractions during inhibin purification.

Evidence for a direct action of acetylcholine on the gastric oxyntic cell of the amphibian

1984 ◽  
Vol 246 (1) ◽  
pp. G16-G25 ◽  
Author(s):  
M. C. Ruiz ◽  
F. Michelangeli
Keyword(s):  
Histamine Release ◽  
Dose Response ◽  
Direct Action ◽  
Second Messengers ◽  
Response Curves ◽  
Experimental Conditions ◽  
Oxyntic Cell ◽  
Endogenous Histamine ◽  
Dual Action ◽  
Dose Response Curves

The possibility of a direct action of acetylcholine (ACh) on the oxyntic cell not mediated by histamine release was studied in resting isolated gastric mucosae. H+ secretion and histamine release, and their relationship, were studied under ACh stimulation and other conditions. ACh released histamine from mucosal stores and stimulated H+ secretion. H2-receptor blocker cimetidine largely inhibited ACh-induced stimulation of H+ transport but not histamine release. Atropine inhibited the cholinergic response in both histamine release and H+ secretion. The dose-response curves to ACh showed nonparallel increases in H+ secretion and histamine release. When dose-response curves to exogenous and endogenous histamine (released by ACh) were compared, it was found that ACh increased Vmax for endogenous histamine. Comparison of the effects of ACh with other experimental conditions such as tetragastrin treatment, K+ depolarization, or Na+-free nutrient solution showed that the amount of histamine released by ACh was insufficient to explain the observed rates of secretion. Stimulation by ACh was faster, greater, and more transitory compared with that by histamine. In mucosae maximally stimulated by histamine, ACh induced a further increase in H+ secretion. In the presence of cimetidine, potentiation between ACh and dibutyryl cAMP or isobutyl-methylxanthine was found. The results are consistent with ACh having a dual action on oxyntic and histamine-releasing cells. The action of ACh on the oxyntic cell would potentiate the effect of released histamine. It is suggested that ACh and released histamine act on the oxyntic cell through different second messengers, resulting in the potentiated response.

Dissociation constants (KA) and relative efficacies of sympathomimetic amines in isolated atria during hypothermia-induced supersensitivity

1983 ◽  
Vol 61 (6) ◽  
pp. 572-580 ◽  
Author(s):  
Kenneth J. Broadley ◽  
John H. McNeill
Keyword(s):  
Dose Response ◽  
Dissociation Constants ◽  
Response Curves ◽  
Isolated Atria ◽  
Adrenoceptor Agonists ◽  
Dose Response Curves ◽  
The Right ◽  
Tension Curves ◽  
Noradrenaline And Adrenaline ◽  
Right Atria

Hypothermia increases the sensitivity of isolated cardiac muscle to stimulation by β-adrenoceptor agonists. The purpose of this study was to determine pharmacologically whether this supersensitivity is associated with a change in the affinity of agonists for the receptor. The positive inotropic and chronotropic responses of guinea-pig paced left and spontaneously beating right atria were recorded. Cumulative dose–response curves to noradrenaline (or adrenaline) were compared with isoproterenol in each tissue. At 38 °C, the rate curves were to the left of the tension curves, with lower mean effective concentration (EC50) values. However, this difference was less for noradrenaline and adrenaline which were therefore tension selective relative to isoproterenol. Lowering the temperature to 25 °C induced supersensitivity, all dose–response curves being displaced to the left. In the presence of carbachol the curves were shifted to the right with depression of the maxima. Dissociation constants (KA) were calculated from plots of reciprocals of equiactive concentrations obtained before and in the presence of carbachol. KA values for rate and tension responses of each agonist were identical at 38 °C, indicating that the rate selectivity was not due to affinity differences. The efficacies (er) of noradrenaline and adrenaline were greater than isoproterenol for tension, but smaller for rate responses, which may explain their relative tension selectivity. At 25 °C the KA values of all agonists were reduced approximately 10-fold. Hypothermia-induced supersensitivity is therefore associated with an increase in affinity for the cardiac β-adrenoceptor.

Biphasic modulation of pituitary sensitivity to GnRH by oestrogens: the effects of A- and D-ring substitution on LH release in cultured pituitary cells

1984 ◽  
Vol 107 (3) ◽  
pp. 317-327 ◽  
Author(s):  
G. Emons ◽  
R. Knuppen ◽  
P. Ball ◽  
K.J. Catt
Keyword(s):  
Dose Response ◽  
High Sensitivity ◽  
Female Rats ◽  
Pituitary Cells ◽  
Response Curves ◽  
Methyl Group ◽  
Lh Release ◽  
Dose Response Curves ◽  
Sensitizing Effect ◽  
Almost All

Abstract. The sensitizing effect of oestrogens on GnRH-stimulated LH release was evaluated in pituitary cells from adult female rats, cultured for 2 days in the presence of 10−13 to 10−6 m concentrations of oestradiol and selected A- and D-ring modified oestrogens. With almost all steroids tested, bell-shaped dose-response curves with comparable LH-maxima but different EDmax values were obtained for the LH response to a submaximal GnRH stimulus (5 × 10−10 m). Maximal LH response to 5 × 10−10 m GnRH were found at the following oestrogen concentrations: oestradiol and 4-hydroxyoestradiol = 10−11 m; 2-methyloestradiol = 10−9 m; 2-hydroxyoestradiol = 10−8 m; with 4-methyloestradiol no significant maximum was observed. When cells were pretreated with 10−13, 10−11 and 10−9 m oestradiol, or 4-hydroxyoestradiol, or 2-hydroxyoestradiol, and exposed to increasing concentrations of GnRH (10−11 to 10−7 m), an almost 10-fold decrease in the ED50 for GnRH was observed after pretreatment with 10−11 m oestradiol and 4-hydroxyoestradiol. With 2-hydroxyoestradiol at this concentration, the sensitizing effect was much less pronounced. Increasing the steroid concentration to 10−9 m slightly decreased the effect of oestradiol and 4-hydroxyoestradiol, whereas it increased the effect of 2-hydroxyoestradiol. Thus, at the target cell 4-hydroxyoestradiol has the same potency as oestradiol, while 2-hydroxyoestradiol is significantly less active. The sensitizing effect of oestradiol is only slightly decreased by the presence of a methyl group in position 2, but is markedly reduced by a methyl group in position 4. Our results also demonstrate the high sensitivity of the pituitary to oestrogen-induced enhancement of GnRH-stimulated gonadotrophin release, as well as the decrease of the positive effect at high oestrogen concentrations. The bell-shaped dose-response curves for oestrogen action should be taken into account when evaluating the effects of oestrogens and their derivatives upon gonadotrophin release from the pituitary gland.

STUDIES ON THE PITUITARY MELANOPHORE-EXPANDING HORMONE WITH REFERENCE TO ITS IDENTITY WITH ACTH

1954 ◽  
Vol 11 (1) ◽  
pp. 7-13 ◽  
Author(s):  
B. KETTERER ◽  
ELIZABETH REMILTON
Keyword(s):  
Linear Regression ◽  
Dose Response ◽  
Progressive Increase ◽  
Regression Curve ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
The Mean ◽  
Dose Response Curves ◽  
Linear Regression Curve

SUMMARY 1. The standard Xenopus method for the assay of pituitary melanophore-expanding hormone has been critically examined, and the results from various assay procedures are statistically analysed. 2. Log dose-response data are well fitted by a linear regression curve. Responses at 3 hr give a steeper curve than those at 1½ hr. 3. Results collected 6 months apart show that the mean and slope of dose-response curves remain constant when Xenopus are given regular dosage; there is, however, a progressive increase of variance with time shown by the colony under these experimental conditions. 4. Evidence is presented to show that Xenopus must be minimally disturbed during assay, and that assay doses must be given not less than 1 day apart.

Analysis and comparison of sigmoidal curves: application to dose-response data

1989 ◽  
Vol 257 (6) ◽  
pp. G982-G989 ◽  
Author(s):  
J. B. Meddings ◽  
R. B. Scott ◽  
G. H. Fick
Keyword(s):  
Nonlinear Regression ◽  
Dose Response ◽  
Numerical Solutions ◽  
Maximal Response ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
Accuracy And Precision ◽  
Analysis Technique ◽  
Dose Response Curves

A number of physiological or pharmacological studies generate sigmoidal dose-response curves. Ideally, data analysis should provide numerical solutions for curve parameters. In addition, for curves obtained under different experimental conditions, testing for significant differences should be easily performed. We have reviewed the literature over the past 3 years in six journals publishing papers in the field of gastrointestinal physiology and established the curve analysis technique used in each. Using simulated experimental data of known error structure, we have compared these techniques with nonlinear regression analysis. In terms of their ability to provide accurate estimates of ED50 and maximal response, none approached the accuracy and precision of nonlinear regression. This technique is as easily performed as the classic methods and additionally provides an opportunity for rigorous statistical analysis of data. We present a method of determining the significance of differences found in the ED50 and maximal response under different experimental conditions. The method is versatile and applicable to a variety of different physiological and pharmacological dose-response curves.

ÜBER DIE DURCH UNSPEZIFISCHE SUBSTANZEN BEDINGTE ÄNDERUNG DER QUANTITATIVEN UND QUALITATIVEN WIRKSAMKEIT VON GONADOTROPINEN BEI DER BIOLOGISCHEN AKTIVITÄTSBESTIMMUNG

1961 ◽  
Vol 38 (2) ◽  
pp. 181-199 ◽  
Author(s):  
K. Walter ◽  
S. Wysocki
Keyword(s):  
Dose Response ◽  
Chorionic Gonadotrophin ◽  
Female Rats ◽  
Response Curves ◽  
Immature Female ◽  
Ovarian Weight ◽  
Immature Rats ◽  
Reference Preparation ◽  
Slope Difference ◽  
Dose Response Curves

ABSTRACT The activity of chorionic gonadotrophin (HCG) injected in solutions containing different nonspecific substances (polyvinylpyrrolidone, gelatine, tragacanth = »depot-media« is compared with the activity of HCG in distilled water. Intact immature female rats are used for the bioassays, which differ only in injection schedule or the response measured (uterine resp. ovarian weight). Depending on the injection schedule used and the response measured the results of the various bioassays in intact immature rats are different, when one and the same depot-medium is used. Significant indices of discrimination as well as significant slope differences of dose-response curves are observed. The addition of a biologically inactive kaolin extract prepared according to the »crude kaolin-acetone method« to a gonadotrophic extract from the urine of postmenopausal women produced a significant decrease in activity in one type of assay, and a significant slope difference of dose-response curves in another one. In view of these results the difficulties arising for the demonstration of qualitative differences in gonadotrophic preparations and for expressing bioassay-results in terms of the International Reference Preparation are discussed.

The β-adrenoceptor site activated by CGP12177 varies in behavior according to the estrous cycle phase and stress

2003 ◽  
Vol 81 (5) ◽  
pp. 459-468 ◽  
Author(s):  
I N Santos ◽  
F K Marcondes ◽  
R C Spadari-Bratfisch
Keyword(s):  
Estrous Cycle ◽  
Stress Hormones ◽  
Serum Levels ◽  
Female Rats ◽  
Cycle Phase ◽  
Response Curves ◽  
Chronotropic Response ◽  
The Right ◽  
Right Atria ◽  
Group Serum

The aim of this work was to assess whether stress and estrous cycle phases affected the β-adrenoceptor (β-AR) site activated by CGP12177 in the right atria of rats. The chronotropic response to CGP12177 in the absence or presence of antagonists was determined in atria from rats submitted to one daily foot-shock session for 3 consecutive days. Blood was collected for hormonal assays. The pD2 for CGP12177 in atria from females was lower than in atria from males and was unaltered by stress or the estrous cycle. Propranolol (200 nM) or CGP20712A (3 μM) shifted the concentration–response curves to CGP12177 to the right in control and stressed estrus or control diestrus rats. Atria from stressed diestrus rats were resistant to blockade by propranolol or CGP20712A, indicating that the effect of β-adrenoceptor antagonists on the response to CGP12177 is influenced by estrous cycle phases. The stress-induced increase in serum corticosterone levels was independent of the estrous cycle or gender, but the estradiol/progesterone ratio was affected differently in the two groups of female rats. In the diestrus group, serum estradiol levels decreased after the first foot-shock session and remained low until the day of sacrifice, whereas in the estrus group the serum levels of estradiol did not decrease after stress and peaked on the second day, which corresponded to proestrus. These data do not indicate whether there is a direct or indirect effect of stress hormones and (or) sex steroids on cardiac β-AR sensitivity. However, they do show that the classic and low-affinity binding sites of the β-AR are independently regulated and that the β-AR atypical site affinity for antagonists depends on the estrous cycle.Key words: allosterism, β-adrenoceptor, β-adrenoceptor, receptor active site, steroid hormones, stress.

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