The Blockade of Angiotensin Action by 8-Leu-Angiotensin on the Guinea-Pig Aortic Strip

1974 ◽  
Vol 52 (2) ◽  
pp. 236-239 ◽  
Author(s):  
P. LeMorvan ◽  
Dj. Palaic ◽  
W. K. Park
Keyword(s):  
Angiotensin Ii ◽  
Guinea Pig ◽  
Dissociation Constant ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Apparent Dissociation Constant ◽  
Aortic Strip ◽  
Potent Antagonist ◽  
The Right

The action of angiotensin on the isolated guinea-pig aortic strip is shown in relation to other agonists. The apparent dissociation constant for angiotensin, as calculated from the dose–response curve, is 6.3 × 10−8 M. The blocking action of 8-Leu-angiotensin II on this preparation is specific for angiotensin since responses to other agonists are not modified. Complete reversibility of the blockade is demonstrated. A parallel shift to the right of the dose–response curve and attainment of maximum response indicate that the antagonism is competitive for angiotensin. It is concluded that 8-Leu-angiotensin II is a highly potent antagonist for angiotensin in this tissue.

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.

Alteration of islet neurotransmitter sensitivity following ventromedial hypothalamic lesion

1983 ◽  
Vol 244 (5) ◽  
pp. R635-R640 ◽  
Author(s):  
L. A. Campfield ◽  
F. J. Smith
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Dose Response ◽  
Response Curve ◽  
Pancreatic Beta Cell ◽  
Dose Response Curve ◽  
Norepinephrine Dose ◽  
Increased Sensitivity ◽  
The Right ◽  
Glucose Responsiveness

Recent studies suggest that alterations in autonomic neural activity may mediate the obese state observed following ventromedial hypothalamic (VMH) lesion. To assess the role of these alterations in the increased glucose responsiveness of the beta-cell observed in this state, we have determined the sensitivity of insulin secretion to norepinephrine or/and acetylcholine in statically incubated pancreatic islets from rats 30-40 days after VMH lesion. In islets from VMH-lesioned rats compared with islets from sham-operated and intact rats, the acetylcholine dose-response curve was shifted down and to the right, indicating a decreased sensitivity, whereas the norepinephrine dose-response curve was translated to the left, indicating an increased sensitivity. The interaction profile, which summarizes combined neurotransmitter exposure on insulin secretion, was shifted in the direction of net inhibition. Thus it was concluded that, following VMH lesion, autonomic neurotransmitter sensitivity of the pancreatic beta-cell was altered. It is suggested that these alterations play a role in the adaptation of the beta-cell to the experimentally induced obese state.

Leukotriene receptor on U-937 cells: discriminatory responses to leukotrienes C4 and D4

1991 ◽  
Vol 261 (2) ◽  
pp. L164-L171 ◽  
Author(s):  
L. A. Wetmore ◽  
N. P. Gerard ◽  
D. K. Herron ◽  
N. G. Bollinger ◽  
S. R. Baker ◽  
...  
Keyword(s):  
Cell Surface ◽  
Dose Response ◽  
Response Curve ◽  
Spatial Configuration ◽  
Dose Response Curve ◽  
Striking Difference ◽  
Cell Surface Receptors ◽  
Leukotriene D4 ◽  
Surface Receptors ◽  
The Right

Dimethyl sulfoxide (DMSO)-differentiated U-937 cells develop cell surface receptors for leukotrienes that, when stimulated, initiate a transient increase in intracellular calcium concentration [( Ca2+]i). We investigated the calcium transient that occurs after addition of leukotriene C4 (LTC4) to determine whether it occurs due to 1) the bioconversion of LTC4 to leukotriene D4 (LTD4), which then acts at the LTD4 receptor; 2) the direct action of LTC4 at the LTD4 receptor; or 3) the action of LTC4 at a receptor selective for LTC4. Bioconversion of [3H]LTC4 to [3H]LTD4 was inhibited by 98% when DMSO-differentiated U-937 cells were incubated with 10 mM AT-125 compared with control cells. The dose-response curve for LTC4, with [Ca2+]i as the index of response, was parallel to that for LTD4 but was significantly (P less than 0.0001) shifted 1.6 +/- 0.11 log units to the right. AT-125 did not change the response to LTD4 but the LTC4 dose-response curve was shifted on additional 1.7 logo units to the right. The antagonists SKF 104353 (1 microM) and LY 171883 (10 microM) shifted the dose-response curve for LTD4 3.0 +/- 0.23 and 2.5 +/- 0.23 log units, respectively, to the right and completely inhibited the change in [Ca2+]i due to LTC4 in the presence of 10 mM AT-125. Molecular modeling studies demonstrated a striking difference in the spatial configuration of LTC4 and LTD4, likely accounting for the ability of cell surface receptors to discriminate between the effects of these two molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Sodium Intake on the Pressor Response to Angiotensin II in the Unanaesthetized Rat

1976 ◽  
Vol 50 (4) ◽  
pp. 285-291
Author(s):  
Barbara L. Slack ◽  
J. M. Ledingham
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Response Curves ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
High Sodium Diet

1. Dose—response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2·5% (w/w) or 0·007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose—response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose—response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose—response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose—response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin—angiotensin system, on the rate of in-activation of angiotensin and on a change in initial length of the muscle fibre.

Histamine Receptors in Normal Human Bronchi

1980 ◽  
Vol 58 (6) ◽  
pp. 537-544 ◽  
Author(s):  
Noemi M. Eiser ◽  
Jane Mills ◽  
K. D. McRae ◽  
P. D. Snashall ◽  
A. Guz
Keyword(s):  
Receptor Antagonist ◽  
Dose Response ◽  
Response Curve ◽  
Normal Subjects ◽  
Dose Response Curve ◽  
Significant Shift ◽  
H2 Receptor Antagonist ◽  
Anticholinergic Activity ◽  
H2 Receptor ◽  
The Right

1. Nine normal subjects inhaled increasing concentrations of histamine aerosol from an aerosol generator attached to a breath-actuated dosimeter. The responses were monitored by measuring specific airways-conductance in a body plethysmograph, and the results were expressed as cumulative log dose-response curves. On separate days, histamine challenges were repeated after intravenous injections of sodium chloride solution (placebo), or an H1-receptor antagonist chlorpheniramine, or an H2-receptor antagonist cimetidine, or H1- and H2-receptor antagonists together. The anticholinergic activity of chlorpheniramine was estimated by comparing the effect of chlorpheniramine and atropine on methacholine challenge. 2. In all subjects the response to histamine was reproducible. Analysis of the variance showed that placebo did not alter the histamine dose-response curve significantly. In contrast, chlorpheniramine produced a large shift in the histamine dose-response curve to the right and cimetidine produced a significant shift of this curve to the right only at the highest dose of histamine. A combination of cimetidine and chlorpheniramine produced a shift not significantly different from that seen with chlorpheniramine alone. Chlorpheniramine showed no significant anticholinergic activity in this study. 3. In the normal subjects histamine-induced bronchoconstriction appeared to be mediated predominantly by the H1-receptors. The H2-receptor contributed very little to this bronchoconstriction.

Postsynaptic potentiation and desensitization in frog neuromuscular junction

1988 ◽  
Vol 66 (5) ◽  
pp. 624-629 ◽  
Author(s):  
M. I. Glavinqvić
Keyword(s):  
Neuromuscular Junction ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Maximal Response ◽  
Frog Neuromuscular Junction ◽  
Receptor Complexes ◽  
Fractional Increase ◽  
The Right ◽  
Postsynaptic Potentiation

The fractional increase in ACh responses that occurs at the beginning of each train of iontophoretically applied ACh pulses has been examined at the frog neuromuscular junction at room temperature, in the presence of active cholinesterase, during desensitization produced by a rapid sequence (every 20 s) of short (5 Hz, 5 s) iontophoretic trains of ACh. The fractional increase in ACh responses, which is used as an indicator of postsynaptic potentiation, becomes progressively greater with ACh application, often markedly (>100%), although ACh responses are greatly reduced (as much as 90%) owing to desensitization. Clearly postsynaptic potentiation can exist concomitantly with desensitization. In addition, the dose–response curve is shifted to the right and its maximal response is diminished. The shift in the dose–response curve to the right, which can explain greater postsynaptic potentiation, is unlikely to be caused by accumulation of "monoligand-bound ACh receptor complexes," since experiments were done with active cholinesterase. The shift probably results from a greater number of desensitized receptors which, because of their large affinity for ACh molecules, serve as "high affinity traps." A small decrease of the maximal dose–response suggests only a small fractional decrease in the number of activable receptors, whereas a large shift to the right indicates a large fractional increase in the number of desensitized receptors. It appears that prior to ACh application only a small fraction of all receptors are desensitized. Alternatively, the shift to the right occurs because the cooperative action of ACh on receptors increases during desensitization.

Desensitisation in Human and Rabbit Blood Platelets

1982 ◽  
Vol 47 (03) ◽  
pp. 278-284 ◽  
Author(s):  
T J Hallam ◽  
P A Ruggles ◽  
M C Scrutton ◽  
R B Wallis
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Blood Platelets ◽  
Human Platelets ◽  
Dose Response Curve ◽  
Maximal Response ◽  
Significant Shift ◽  
Type I ◽  
Rabbit Blood ◽  
The Right

Summary1. Exposure of human and rabbit blood platelets to all full agonists tested induces agonist-specific (or homologous) desensitisation except in the case of adrenaline and collagen in human platelets.2. Desensitisation to vasopressin and 5-hydroxytryptamine (5HT) develops rapidly and results from suppression of maximal responsiveness without significant shift in the dose/response curve (Type I). In rabbit platelets, maintenance of desensitisation to 5HT is correlated with the extracellular 5HT concentration. Responsiveness to other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without change in maximal responsiveness.3. Homologous desensitisation to ADP, U-46619 and thrombin develops more slowly, is correlated with disaggregation and is associated with a shift in the dose/response curve to the right without suppression of maximal responsiveness (Type II). Responsiveness to most other agonists is either unaffected, or is enhanced due to a shift in the dose/response curve to the left without a change in maximal responsiveness. However, exposure to thrombin suppresses the maximal response to vasopressin without a shift in the dose/response curve, and exposure to U-46619 causes a shift in the dose/response curve for collagen to the right.4. In human platelets prolonged exposure to 5HT causes agonist non-specific (or heterologous) desensitisation in which responsiveness to all agonists except adrenaline is suppressed as a result of shifts in the dose/response curves to the right.5. We propose that Types I and II homologous desensitisation result respectively from prolonged receptor occupancy and from either activation of degradative mechanisms for the agonist or processing of the receptor to a lower affinity state.

Forskolin stimulation of naphthylamidase in guinea pig thyroid sections detected with a cytochemical bioassay

1985 ◽  
Vol 108 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Patricia A. Ealey ◽  
Leonard D. Kohn ◽  
Nicholas J. Marshall ◽  
Roger P. Ekins
Keyword(s):  
Guinea Pig ◽  
Dose Response ◽  
Response Curve ◽  
Thyroid Tissue ◽  
Receptor Site ◽  
Dose Response Curve ◽  
Cytochemical Bioassay ◽  
Surface Receptor ◽  
Stimulation Of ◽  
Endocrine Tissues

Abstract. Forskolin, from the roots of the Indian medicinal plant Coleus forskohlii, has recently been shown to be a potent stimulator of adenylate cyclase in many systems, including endocrine tissues such as the thyroid gland. We describe forskolin activation of β-naphthylamidase activity in guinea pig thyroid tissue using the cytochemical bioassay (CBA) for thyroid stimulators. This CBA is the most sensitive bioassay for TSH and LATS-B currently available, being able to detect stimulation by doses as low as 10−5 mU TSH/l and 10−9 mU LATS-B/l. The dose-response curve to forskolin was bell-shaped (as is seen with TSH and LATS-B) with the ascending limb of the curve produced by 10−13 m to 10−12 m forskolin after a 3 min exposure time. Maximal stimulation was observed with 10−12m forskolin. However, the dose-response curve to forskolin was not parallel to that given by TSH, the slope of the ascending limb being much greater. It has been suggested that stimulation of β-naphthylamidase activity in the CBA is via cAMP. We report that dibutyryl cAMP at doses from 10−16m to 10−11 m produces a bell-shaped dose-response curve with a very broad peak response, again not parallel to that produced by TSH. Forskolin activation of β-naphthylamidase in the CBA is unaffected by a 1:106 dilution of 11E8, a monoclonal antibody raised against solubilised TSH receptors, which binds to the TSH receptor and inhibits TSH stimulation. Although the precise location of forskolin action is not known, this is further evidence that forskolin acts at a post-surface receptor site.

Role of Endothelial K + Channels in NO-Dependent Vasorelaxant Responses to Acetylcholine in Rat Aorta.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 698-698
Author(s):  
John Quilley ◽  
Yue Qiu
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Rat Aorta ◽  
Dose Response Curve ◽  
Response Curves ◽  
K Channels ◽  
Voltage Dependent ◽  
The Right ◽  
Stimulation Of

P30 Endothelium-dependent vasorelaxant responses to acetylcholine (Ach) in rat aorta are mediated solely by NO. Rings precontracted with U46619 were used to investigate the role of endothelial K + channels. Thus, any effect of K + channel inhibitors on Ach responses in the absence of an effect on those to nitroprusside (NP) can be attributed to interference with Ach-induced stimulation of NO. Vasorelaxant responses to Ach (log EC 50 -7.29M) were abolished by removal of the endothelium or inhibition of NO synthesis with nitroarginine (100μM) which potentiated responses to NP (log EC 50 -9.41M vs -8.47M for control). In the presence of TEA (10mM) to inhibit K + channels, the dose-response curve for Ach, but not NP, was shifted to the right (log EC 50 -6.06). Elevation of extracellular K + (25mM KCl)also shifted the dose-response curve for Ach to the right. Inhibitors of specific types of K + channels: BaCl 2 (30μM), apamin (100nM), glibenclamide (10μM), charybdotoxin (50nM) and iberiotoxin (100nM) were without effect on dose-response curves to either Ach or NP. However, the combination of apamin (100nM) and charybdotoxin (50nM) but not apamin plus iberiotoxin, reduced relaxant responses to Ach (log EC 50 -6.95M) without affecting those to NP.These results confirm that Ach-induced relaxation of rat aorta is mediated entirely by endothelium-derived NO, the release of which apparently involves hyperpolarization of the endothelium. This effect is dependent on activation of a K + channel that is blocked by a combination of apamin/charybdotoxin but neither agent alone, possibly indicating characteristics of both Ca 2+ - activated and voltage-dependent K + channels.

The Effect of Vagotomy on the Lower Part of the Acid Dose-Response Curve to Pentagastrin in Man

1972 ◽  
Vol 43 (2) ◽  
pp. 193-200 ◽  
Author(s):  
J. B. Elder ◽  
G. Gillespie ◽  
E. H. G. Campbell ◽  
I. E. Gillespie ◽  
G. P. Crean ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Dose Response ◽  
Response Curve ◽  
Response Pattern ◽  
Positive Response ◽  
Dose Response Curve ◽  
Threshold Dose ◽  
Truncal Vagotomy ◽  
Small Doses ◽  
The Right

1. The acid secretory responses to insulin of forty-seven duodenal ulcer patients after truncal vagotomy and drainage were classified according to the criteria of Hollander (1946) into positive or negative. 2. The acid response to ranges of small doses of pentagastrin was studied in these two groups. In the group with a positive acid response after insulin the dose-response pattern to pentagastrin was very similar to that in preoperative patients. 3. In those who failed to satisfy criteria for a positive response after insulin the dose-response curve to pentagastrin appeared to shift to the right. It had a lower level and a smaller slope. Truncal vagotomy appeared to cause an eightfold increase in the threshold dose found in preoperative patients. 4. Supersensitivity of the stomach to small doses of pentagastrin after vagotomy was not apparent in the present study.

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