The Effect of Ovarian Hormones on the Contractility of the Rabbit Oviductal Isthmus

1974 ◽  
Vol 52 (1) ◽  
pp. 74-83 ◽  
Author(s):  
G. W. Higgs ◽  
A. H. Moawad
Keyword(s):  
Dose Response ◽  
Adrenergic Receptors ◽  
Additional Treatment ◽  
Beta Receptor ◽  
Low Concentrations ◽  
Alpha Receptors ◽  
Circular Rings ◽  
Tension Increase ◽  
The Right

In order to investigate the phenomenon of "tubal locking" of ova, the in vitro contractility of circular rings from the rabbit oviductal isthmus was examined in different hormonal states. Both alpha and beta adrenergic receptors were found to be present in this preparation with predominance of the alpha receptors when the tissues were from either estrogen- or progesterone-dominant animals.Progesterone treatment of estrogen-primed, immature females influenced the dose–response curve of the circular oviductal muscle to norepinephrine, significantly shifting it to the right, in comparison with tissues from animals that had been treated with estrogen only. There was less of a shift when dose–response relations were determined for phenylephrine after beta receptor blocked with propranolol, suggesting that progesterone enhanced the responses of beta compared with alpha receptors. However, there was still a small difference between responses of estrogen- and progesterone-dominated tissue, at least at low concentrations. Since beta receptor activity had been effectively eliminated, this tendency suggests that progesterone's effect on the response to norepinephrine is not completely due to a modification in beta receptor activity.The spontaneous contractility of tissues from estrogen-treated animals was characterized by a series of rapid spike-like contractions with fairly consistent shape and frequency. Additional treatment with progesterone modified the pattern to an irregular one. Moreover, the total spontaneous activity of muscle from estrogen-dominant animals (as measured by the area under the contractility curve) was significantly reduced, and the rate of tension increase was considerably slower than that from animals with progesterone as the dominant hormone. This indicated a form of antagonism to estrogen by progesterone not involving adrenergic receptors.Maximal excitation of the strips with nonspecific agents or adrenergic agonists resulted in significantly less activity in tissues from progesterone-treated animals. The mechanism of action of progesterone to produce this effect probably involves a step or steps in the excitation–contraction process beyond the adrenergic receptors.

Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine

1979 ◽  
Vol 57 (1) ◽  
pp. 35-40 ◽  
Author(s):  
S. C. Cunnane ◽  
H. Zinner ◽  
D. F. Horrobin ◽  
M. S. Manku ◽  
R. O. Morgan ◽  
...  
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Biological Action ◽  
Dose Response Curve ◽  
Low Concentrations ◽  
Pressor Responses ◽  
The Right ◽  
Copper Effect

Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 × 10−6 M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose–response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 × 10−11 M PGE1 and to the left by 2.8 × 10−7 M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose–response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.

Characterization of sulfidopeptide leukotriene responses in sheep tracheal smooth muscle in vitro

1991 ◽  
Vol 69 (6) ◽  
pp. 805-811 ◽  
Author(s):  
K. Tomioka ◽  
J. T. Jackowski ◽  
W. M. Abraham
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Tracheal Smooth Muscle ◽  
Response Curves ◽  
Leukotriene Antagonist ◽  
Dose Response Curves ◽  
The Right ◽  
Glutamyl Transpeptidase

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100 μM. Indomethacin (5 μM) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of γ-glutamyl transpeptidase, shifted the dose–response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose–response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1 μM), an LT antagonist, shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1 μM) shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.87 and 7.31, respectively. YM-17690 (10 μM) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.Key words: leukotriene antagonist, receptors, asthma.

ANG II- and TxA2-induced mesenteric vasoconstriction in rats is mediated by separate cell signaling pathways

1999 ◽  
Vol 277 (1) ◽  
pp. H1-H7 ◽  
Author(s):  
Johannes Bauer ◽  
Cécile Dau ◽  
Alessandro Cavarape ◽  
Franz Schaefer ◽  
Heimo Ehmke ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Dose Response ◽  
Ang Ii ◽  
Response Curves ◽  
Intracellular Ca ◽  
The Right ◽  
Activate Protein Kinase ◽  
Cell Signaling Pathways

Studies in vitro have demonstrated that vasoconstrictor agents increase intracellular Ca2+ and activate protein kinase C (PKC) to elevate vascular tone. The aim of the present study was to determine the importance of these signaling pathways for angiotensin II (ANG II) and thromboxane A2(TxA2) in regulating mesenteric blood flow (MBF) in vivo. In anesthetized rats increasing doses of ANG II or the TxA2 agonist U-46619 were administered into the superior mesenteric artery to reduce MBF. Intra-arterial infusion of inhibitors served to examine the contribution of different pathways: 8-(diethylamino)octyl 3,4,5-trimethoxybenoate hydrochloride (TMB-8) to inhibit intracellular Ca2+ release, nifedipine to block transmembrane Ca2+ influx through the L-type Ca2+ channel, and staurosporine to inhibit PKC. Each of the inhibitors attenuated ANG II-induced reductions in MBF, and all dose-response curves were shifted to the right to an approximately threefold higher ANG II dose. Combinations of the inhibitors revealed that their effects were additive; together they abolished the vasoconstrictor action of ANG II completely. In contrast, the dose-response curve for U-46619 was not affected by any of the inhibitors infused either separately or together. The results demonstrate that a rise in intracellular Ca2+ and activation of PKC are major mediators of the vasoconstrictor effect of ANG II in mesenteric circulation, but they play a subordinate role, if any, for the effects of TxA2. Because TxA2 plays a major role only under pathological conditions, the uncontrolled vasoconstriction appears to be associated with the recruitment of novel signal transduction pathways.

Human and rat airway smooth muscle responsiveness after ozone exposure in vitro

1996 ◽  
Vol 271 (4) ◽  
pp. L631-L636 ◽  
Author(s):  
E. Roux ◽  
C. Guibert ◽  
H. Crevel ◽  
J. P. Savineau ◽  
R. Marthan
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Dose Response ◽  
Ex Vivo ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Maximal Response ◽  
The Right ◽  
Rat Trachea

We previously reported that NO2 and acrolein administered ex vivo to the lung altered the subsequent responsiveness of airway smooth muscle. The aim of this study was to determine the dose-response relationship for O3 in both human isolated bronchi and rat tracheae and to investigate the mechanisms underlying O3-induced airway responsiveness. Exposure to 1 ppm O3 for 15 min significantly increased the maximal response to carbachol of rat tracheal rings to 149.6 +/- 5.4% of the reference response to acetylcholine (ACh) compared with that of unexposed rings (131.3 +/- 2.4%, n = 6, P < 0.05). The change in maximal airway responsiveness to carbachol, when plotted against the product of exposure concentration and exposure time to O3, a surrogate for the dose, formed a bell-shaped curve. The peak of this dose-response curve was shifted to the right for human bronchi (50 ppm x min, n = 5) compared with that of rat tracheae (15 ppm x min, n = 6). In the rat trachea, responses to KCl were not altered by O3, whereas those to 5-hydroxytryptamine hydrochloride (5-HT) were significantly increased. Finally, in the absence of external Ca2+, O3 exposure still potentiated the maximal response to carbachol from 73.6 +/- 13.9 to 137.0 +/- 6.0% and that to 5-HT from 21.5 +/- 5.5 to 38.7 +/- 2.2% of the reference ACh response. These results indicate that O3 alters the subsequent in vitro airway responsiveness depending on 1) the dose, 2) the nature of the agonist, and 3) the species investigated. Because in vitro exposure to O3 increases responses to agonists that release intracellular Ca2+ and since this effect is maintained in Ca(2+)-free solution, the mechanism of O3-induced increase in airway smooth muscle responsiveness is likely to involve an enhancement in intracellular Ca2+ release.

RELEASE OF THYROTROPHIN IN VIVO AND IN VITRO BY SYNTHETIC NEUROHYPOPHYSIAL HORMONES

1964 ◽  
Vol 42 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Frank S. LaBella
Keyword(s):  
Dose Response ◽  
In Vitro Release ◽  
Optimal Level ◽  
Response Curves ◽  
Low Concentrations ◽  
Pituitary Glands ◽  
In Vivo Effects ◽  
Synthetic Oxytocin

The influence of synthetic oxytocin and synthetic lysine-8-vasopressin on the release of thyrotrophin (TSH) from slices of the "basophilic" zone of bovine anterior pituitary glands was determined. Up to 10-fold stimulation of TSH release occurred in the presence of the peptide hormones at low concentrations (approximately 10−11 to 10−9 M). Concentrations greater than 10−9 M were less stimulatory, ineffective, or inhibitory. In general, vasopressin stimulated at lower concentrations than did oxytocin. The dose–response curve of oxytocin began to descend at lower concentrations than did that of vasopressin.Stimulation of I131 discharge from the thyroids of propylthiouracil (PTU)-treated, day-old chicks was produced by the intraperitoneal injection of as little as 4 ng vasopressin or 25 ng oxytocin. As the injected dose of either peptide was increased beyond an optimal level, there was less enhancement of I131 discharge, and, with further increases, inhibition. The decreasing response began with lower doses of oxytocin than of vasopressin. The similarities of the dose–response curves of thyroid I131 discharge and of in vitro release of TSH indicate that the in vivo effects of injected neurohypophysial peptides are mediated through the release of endogenous TSH.

scholarly journals In vitro tracheospasmolytic effect and acute toxicity screening of Coptosapelta flavescens Korth root ’s water extract

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 949-954
Author(s):  
Khemasili Kosala ◽  
Sjarif Ismail ◽  
Ika Fikriah ◽  
Yovita Gunawan
Keyword(s):  
Daphnia Magna ◽  
Adrenergic Receptors ◽  
Lethal Dose ◽  
Water Extract ◽  
Relaxation Mechanism ◽  
Tracheal Ring ◽  
Artemia Salina ◽  
Toxicity Screening ◽  
The Right

There are no data available regarding the bronchospasmolytic activity and toxicity of water extract of Coptosapelta flavescens Korth root (WECFR). Therefore, this study aimed to determine: a. the in vitro tracheospasmolytic effect of WECFR; b. safety of WECFR using the brine shrimp lethality test (BSLT) and immobilization of Daphnia magna larvae (IDL). In study, a guinea pig tracheal ring was contracted with methacholine and cumulative doses of WECFR solution were administered. A dose-response curve (DRC) was plotted of the percentage of the tracheal ring relaxation response. To test whether the relaxation mechanism occured through stimulation of beta2-adrenergic receptors, the tracheal ring was incubated with propranolol. Data analyzed using analysis of variance, showed that the DRC of WECFR was obtained with p < 0.05 compared to the DRC of control, indicating that WECFR had a tracheospasmolytic effect. The DRC for propranolol-blocked WECFR did not shift to the right compared to the DRC of WECFR, confirming that the relaxation mechanism did not occur through the beta2-adrenergic receptors. Study b. assessed safety using BSLT and IDL. After exposing the larvae to WECFR and control for 24 and 48 h, respectively, the number of dead larvae was counted. Data analyzed using Probit program, showed that the lethal dose 50 of WECFR towards Artemia salina and Daphnia magna larvae was > 1000 ppm, which means that it was not toxic. This studies demonstrate that WECFR exhibits tracheospasmolitic effect, but not through beta2-adrenergic receptors; WECFR is safe for Artemia salina and Daphnia magna larvae.

Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR

1992 ◽  
Vol 262 (5) ◽  
pp. C1284-C1291 ◽  
Author(s):  
J. G. Pickar ◽  
S. D. Gray ◽  
R. C. Carlsen
Keyword(s):  
Adrenergic Receptors ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Catecholamines ◽  
Skeletal Muscle Function ◽  
Extracellular Medium ◽  
Membrane Hyperpolarization ◽  
Spontaneously Hypertensive ◽  
Alpha Receptors ◽  
Wistar Kyoto

The depressed functional capabilities of spontaneously hypertensive rat (SHR) muscles, reported previously (Exp. Neurol. 95: 249-264, 1987), may reflect a decrease in muscle responsiveness to catecholamines occurring as a consequence of exposure to the elevated level of plasma catecholamines in SHR. Responsiveness to applied catecholamines was determined in SHR and Wistar-Kyoto rat (WKY) soleus by measuring muscle resting membrane potentials (RMP) in vitro. Epinephrine (10(-6) M) produced a similar membrane hyperpolarization in SHR and WKY fibers. Pretreatment with the beta-antagonist propranolol completely blocked the epinephrine-induced hyperpolarization in WKY, but not in SHR. SHR soleii from both young and old rats contained a population of alpha 1-adrenergic receptors also associated with membrane hyperpolarization. The alpha-receptors appeared to be associated with a ligand-gated Ca(2+)-influx pathway, since the alpha-agonist-induced membrane hyperpolarization required the presence of Ca2+ in the extracellular medium. The alpha-induced hyperpolarization was also blocked by apamin, a derivative of bee venom which blocks a Ca(2+)-activated K(+)-efflux pathway in a variety of tissues. The possible role of these novel alpha-receptors in skeletal muscle function, and their relationship to the development of hypertension, is uncertain.

Catecholamines stimulate testicular testosterone release of the immature golden hamster via interaction with alpha- and beta-adrenergic receptors

1992 ◽  
Vol 127 (6) ◽  
pp. 526-530 ◽  
Author(s):  
A Mayerhofer ◽  
RW Steger ◽  
G Gow ◽  
A Bartke
Keyword(s):  
Receptor Antagonist ◽  
Golden Hamster ◽  
Adrenergic Receptors ◽  
Synergistic Effects ◽  
Beta Adrenergic Receptors ◽  
Stimulatory Action ◽  
Beta Adrenergic ◽  
Testosterone Production ◽  
Beta Receptor

Several lines of evidence suggest that catecholamines are involved in the regulation of the development of the testis. We have therefore investigated the ability of testicular parenchyma (decapsulated pieces of testes) from 18 to 20-day-old golden hamsters to respond to catecholaminergic stimuli in vitro. Norepinephrine and epinephrine, as well as the beta-receptor agonist isoproterenol and the alpha-adrenoreceptor agonist phenylephrine were able to significantly stimulate testicular testosterone production. Dopamine and serotonin were not effective. The stimulatory action of norepinephrine on testosterone production was dependent on the concentration. In incubations of testes with human chorionic gonadotropin (hCG) and norepinephrine, no synergistic effects on testosterone release were observed. The stimulatory effect of norepinephrine could be partially blocked by incubation with beta-receptor antagonist propranolol, or with alpha-receptor antagonist prazosin, while a combination of propranolol and prazosin completely inhibited the norepinephrine-induced testosterone production. Moreover, isoproterenol and phenylephrine in combination stimulated testosterone more than either drug did alone. Measurements of concentrations of norepinephrine and epinephrine in testicular homogenates revealed higher values for these catecholamines than in the plasma, implying that catecholamine levels in the interstitial spaces of the testis might be in the range of concentrations effectively stimulating testosterone production in vitro. This suggests that in the immature testis of the golden hamster, catecholamines acting through both alpha- and beta-adrenergic receptors may be potent physiological stimulators of testosterone production.

scholarly journals Folate requirements of methotrexate-resistant human acute lymphoblastic leukemia cell lines

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 586-591 ◽  
Author(s):  
Y Kano ◽  
T Ohnuma ◽  
JF Holland
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Growth ◽  
Dose Response ◽  
Response Curve ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Collateral Sensitivity ◽  
The Right ◽  
Human Acute Lymphoblastic Leukemia

Abstract We studied the folate requirements of a human acute lymphoblastic leukemia cell line, MOLT-3, and methotrexate (MTX)-resistant sublines established in vitro. The requirement of pteroylglutamate (PGA) for optimal cell growth was different for each cell line. With increasing MTX resistance, there was progressive increase in PGA requirements, moving the PGA concentration-cell growth curve (dose-response curve) 1 log order of magnitude to the right. The increases in the requirement of 5-methyltetrahydrofolate (5-methyl-THF) by the resistant sublines were more pronounced than PGA requirement, moving the dose-response curve nearly 3 log orders in magnitude to the right. The concentrations in vitro of 5-methyl-THF required for optimal growth of the MTX- resistant sublines far exceeded the normal serum 5-methyl-THF concentrations known in humans. These observations show that MTX- resistant cell established in vitro in culture media containing PGA instead of 5-methyl-THF, a physiological folate, cannot be expected to grow in vivo. The collateral sensitivity of transport-impaired MTX- resistant sublines to 2,4-diamino-5-methyl-6-[(3',4',5'- trimethoxyanilino) methyl] quinazoline (trimetrexate, TMQ) was negated in the absence of PGA. With the addition of 5-methyl-THF, the parent cells became more resistant than the transport-impaired sublines to TMQ These data indicate that the collateral sensitivity of MTX resistant cells to the substituted 2,4-diaminoquinazoline is due to functional folate deficiency by virtue of the impaired transport of folate.

EFFECTS OF OXYTOCIN ON THE UTERINE RESPONSE TO ELECTRICAL STIMULATION

1962 ◽  
Vol 41 (2) ◽  
pp. 161-169 ◽  
Author(s):  
N. Wiqvist ◽  
I. Wiqvist ◽  
C. A. Fielitz ◽  
R. Caldeyro-Barcia
Keyword(s):  
Electrical Stimulation ◽  
Dose Response ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Rat Uterus ◽  
Experimental Conditions ◽  
Minimum Effective Concentration ◽  
Low Concentrations ◽  
Tenfold Increase

ABSTRACT The enhancing effect of low concentrations of oxytocin on the uterine response to electrical stimulation was measured »in vitro« on the superfused rat uterus. In order to reduce the incidence of spontaneous motility, the pacemaker areas were excised from the uterine strip and the calcium concentration was lowered to 1/5th of that of a normal Krebs solution. Under these experimental conditions, it was found that the minimum effective concentration of oxytocin was generally between 5 and 20 μU/ml. A graded dose-response relationship was obtained within a range of concentrations from 5 to 50 μU/ml; within this range, a tenfold increase of the oxytocin concentration caused a five-fold augmentation of the uterine response. The possible use of this method for the bioassay of oxytocin is discussed. Both the range of oxytocin concentrations employed as well as the dose-response relationship found in this investigation for the superfused rat uterus bear a suggestive resemblance to the results published by others for the response of the pregnant human uterus »in situ« to the intravenous infusion of oxytocin.

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