Inhibition of eledoisin by morin on the isolated guinea pig ileum

1968 ◽  
Vol 46 (1) ◽  
pp. 67-69 ◽  
Author(s):  
André L. Gascon
Keyword(s):  
Blood Pressure ◽  
Guinea Pig ◽  
Dose Response ◽  
The Other ◽  
Guinea Pig Ileum ◽  
Response Curves ◽  
Rat Blood ◽  
Other Hand ◽  
Noncompetitive Inhibitor ◽  
Dose Response Curves

The response of the isolated guinea pig ileum to angiotensin, bradykinin, eledoisin, and acetylcholine was studied before and during exposure to morin. Dose–response curves were made for each agonist in the presence of different concentrations of the flavonoid (1 to 8 μg/ml). Under these conditions, the responses of the ileum to eledoisin, angiotensin, and acetylcholine were modified to various degrees depending upon the concentration of morin. With morin 1 μg/ml, the effect of eledoisin was reduced, and the activity of this polypeptide progressively decreased with an increase in the concentration of the inhibitor. On the other hand, the activity of acetylcholine was potentiated while that of bradykinin and angiotensin was unchanged. With higher concentrations of morin (4 and 8 μg/ml), the effect of both angiotensin and acetylcholine was slightly reduced. On the rat blood pressure, morin did not modify the effect of agonists. From these results it is concluded that morin is a specific and noncompetitive inhibitor of eledoisin on the isolated guinea pig ileum.

Effects of epinephrine and Ca on contractile strength and Ca45 exchange in rabbit atria

1960 ◽  
Vol 199 (4) ◽  
pp. 609-612 ◽  
Author(s):  
Arthur H. Briggs ◽  
William C. Holland
Keyword(s):  
Dose Response ◽  
The Other ◽  
Response Curves ◽  
Essential Component ◽  
The Media ◽  
Noncompetitive Inhibitor ◽  
Dose Response Curves ◽  
Rabbit Atria

A comparison of the effects of Ca and epinephrine on contractile tension changes and Ca45 exchange in isolated rabbit atria was made. Dose response curves of Ca were determined with and without epinephrine (2.7 x 10–5 m) and dose response curves of epinephrine were determined with three concentrations of Ca in the media (0.3 mm, 2.4 mm and 9.6 mm) at both pH 6.9 and pH 7.75. Epinephrine enhanced the effect of a given concentration of Ca two to three times in a competitive manner. However, Ca acted as a noncompetitive inhibitor on the response of atria to epinephrine. Ca45 studies revealed that epinephrine decreased Ca influx. This effect was enhanced by increasing the extracellular Ca concentration. Ca45 efflux was not affected by epinephrine. Increasing the pH acted similar to epinephrine. These data suggest that epinephrine increases contractile strength of the heart by at least two mechanisms, one involving an increased binding of calcium in the membrane (competitive), the other involving a noncompetitive antagonism, perhaps of another essential component in the reaction, such as Mg++.

The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy

1987 ◽  
Vol 72 (3) ◽  
pp. 351-357 ◽  
Author(s):  
F. Broughton Pipkin ◽  
R. Morrison ◽  
P. M. S. O'Brien
Keyword(s):  
Blood Pressure ◽  
Dose Response ◽  
Prostaglandin E1 ◽  
Age Groups ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Hormonal Response ◽  
Response Curves ◽  
Basal Blood Pressure ◽  
Dose Response Curves

1. The effect of prostaglandin E1 (PGE1) on the pressor and hormonal response to angiotensin (ANG) II has been studied in 22 women in second trimester pregnancy. Three-point dose–response curves were initially determined for all women. Eleven then received an infusion of PGE1 while the remainder received an infusion of normal saline as controls. The dose–response curves to ANG II were re-studied after a period of stabilization. 2. Although assignation to treatment group was random, differences were found in age and basal blood pressure between the control group and those given PGE1. The pressor data from the PGE1 group were thus split by age for analysis. 3. The administration of ANG II alone was associated with significant (P<0.001 at all doses) pressor effects without accompanying bradycardia. Plasma renin concentration (PRC) was suppressed (P<0.001). Plasma aldosterone concentration rose (P<0.001), the magnitude of the rise being directly associated with the plasma ANG II concentrations achieved (P<0.05). 4. The infusion of PGE, had no significant effect on basal blood pressure, but evoked a sustained tachycardia in both age groups (P<0.001). Basal hormone concentrations were unchanged. 5. The pressor response to ANG II was blunted in the presence of PGE1, in both age groups, the overall effect being greatest when the initial response had been large (P<0.05). Measured plasma concentrations of ANG II were lower under these circumstances (P<0.02). PRC fell (P<0.05 for both groups) and plasma aldosterone concentrations rose (P<0.005 for the treated and P<0.001 for the control groups), but the magnitude of these changes did not differ significantly in the two groups. 6. These data support the hypothesis of a for the vasodilator prostaglandins in minimizing the potential pressor effects of the raised ANG II concentrations seen in pregnancy.

Experimental Study of Reversibility of a Diazepam Overdose by Physostigmine or Galanthamine

1985 ◽  
Vol 1 (S1) ◽  
pp. 287
Author(s):  
George Havasi ◽  
Jonas Gintautas ◽  
Philip R. Warren ◽  
Ilona Hayasi ◽  
Barry J. Kraynack
Keyword(s):  
Experimental Study ◽  
Dose Response ◽  
Antagonistic Effect ◽  
The Other ◽  
Response Curves ◽  
Suicidal Attempts ◽  
Dose Response Curves ◽  
Pain Stimuli ◽  
Galanthamine Hydrobromide

Diazepam is a commonly used drug for suicidal attempts. The antagonistic effect of physostigmine in these patients is poorly understood.We studied the interaction of large doses of diazepam and either physostigmine or galanthamine hydrobromide using dose-response curves in 21 cats. After establishing dose-response curves for diazepam, half of the animals received 0.02 mg/kg of physostigmine intravenously. Two minutes later 8, 10, 12, or 14 mg/kg of diazepam was administered intravenously. After 2, 5, and 10 min, animals were evaluated for their response to noise and pain stimuli. The other half of animals were given 0.2 mg/kg of galanthamine intravenously and evaluated for diazepam effect using the same criteria. Sufficient number of days were allowed for the animals to recover from diazepam.

scholarly journals New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure.

2007 ◽  
Vol 54 (1) ◽  
pp. 193-198 ◽  
Author(s):  
Olga Labudda ◽  
Tomasz Wierzba ◽  
Dariusz Sobolewski ◽  
Małgorzata Sleszyńska ◽  
Łukasz Gawiński ◽  
...  
Keyword(s):  
Blood Pressure ◽  
The Other ◽  
Rat Uterus ◽  
Rat Blood ◽  
Other Hand ◽  
N Terminus ◽  
Pressure Lowering ◽  
Bradykinin Analogues ◽  
Group D

Our previous studies suggested that acylation of the N-terminus of several known B2 antagonists with various kinds of bulky acyl groups consistently improved their antagonistic potency in rat blood pressure assay. On the other hand, our earlier observations also seemed to suggest that the effects of acylation on the contractility of isolated rat uterus depended substantially on the chemical character of the acyl group, as we observed that this modification might either change the range of antagonism or even transform it into agonism. Bearing all this in mind, we decided to synthesize seven new analogues of bradykinin by N-terminal acylation with various acyl groups of a moderately potent B2 antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe-Thi-Arg. The analogues were tested in vitro for their blood pressure-lowering and uterotonic activities. The modifications either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, all seven substituents negatively influenced the interaction with the rat uterine receptors. Our results may be helpful for designing new B2 agonists and antagonists.

An Investigation of the Prolonged Pressor Response to Renin in the Nephrectomized Rat

1976 ◽  
Vol 51 (s3) ◽  
pp. 151s-153s ◽  
Author(s):  
G. W. Boyd
Keyword(s):  
Blood Pressure ◽  
Dose Response ◽  
Pressor Response ◽  
Pressure Increase ◽  
Angiotensin I ◽  
Response Curves ◽  
Blood Pressure Increase ◽  
Dose Response Curves

1. In an investigation of the prolonged pressor response to renin that develops after nephrectomy, angiotensin I dose—response curves and rat renin clearances were studied in nephrectomized rats and paired sham-nephrectomized control animals under pentobarbitone anaesthesia. 2. Both threshold and slope of the angiotensin I dose—response curves were decreased at 15–27 h after nephrectomy. 3. The ratio of renin clearance (determined during renin infusions) in the nephrectomized rat to that in the paired sham-nephrectomized control animals was 0·49 ± 0·03 (sem), P < 0·001 (n = 12 pairs). 4. Both factors contribute towards the prolongation of the blood pressure increase after intravenously administered renin in the nephrectomized animal.

Ca2+ utilization in guinea pig ileal longitudinal smooth muscle in response to a series of muscarinic agonists

1979 ◽  
Vol 57 (12) ◽  
pp. 1375-1380 ◽  
Author(s):  
L. B. Rosenberger ◽  
D. J. Triggle
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Dose Response ◽  
Mechanical Response ◽  
Contractile Response ◽  
Muscarinic Agonists ◽  
Response Curves ◽  
Partial Agonists ◽  
Ca Uptake ◽  
Dose Response Curves

45Ca uptake associated with the mechanical responses to a series of muscarinic agonists including carbachol, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide, and three related 1,3-dioxolanes, including full and partial agonists, has been measured. Generally good agreement is found between the dose–response curves for 45Ca uptake and mechanical response, indicating that the processes of 45Ca entry, believed to be mediated through Ca2+ channels, and contractile response are closely linked. Consistent with this, partial agonists show (relative to full agonists) a reduced 45Ca uptake. The dose–response curves for carbachol-mediated contractile response and 45Ca uptake are compared with available literature data for carbachol action in the guinea pig ileal smooth muscle including binding, depolarization, and phosphatidylinositol turnover.

The Effect of Dietary Sodium Intake on the Blood Pressure and Cardiac Output Responses to Angiotensin II in Unanaesthetized Rats

1977 ◽  
Vol 52 (6) ◽  
pp. 571-576
Author(s):  
Barbara L. Slack ◽  
J. M. Ledingham
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Angiotensin Ii ◽  
Dose Response ◽  
Sodium Intake ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Response Curves ◽  
Low Sodium ◽  
Dose Response Curves

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 and administered in various sequences. 2. Dose—response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose—response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.

Structure–activity studies on substance P

1979 ◽  
Vol 57 (12) ◽  
pp. 1427-1436 ◽  
Author(s):  
R. Couture ◽  
A. Fournier ◽  
J. Magnan ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Blood Pressure ◽  
Substance P ◽  
Guinea Pig ◽  
Free Acid ◽  
Biological Activities ◽  
Intrinsic Activity ◽  
Guinea Pig Ileum ◽  
Rat Blood ◽  
Mesenteric Vein ◽  
Structure Activity

A complete series of analogues of substance P (SP) in which L-Ala was used to replace the natural residues one by one, and the C-terminal free acid SP, were synthesized and tested in order to study the relationships between chemical structure and biological activities. All compounds were tested for their hypotensive effect on the rat blood pressure and for their myotropic activities on the guinea pig ileum, the rabbit anterior mesenteric vein, and the rat vas deferens.The results indicate that the first five residues from the amino end and Gly9 can be replaced by L-Ala without change of hypotensive or myotropic activities, but the substitution of the residues from the carboxyl end (Met11, Leu10, Phe8, and Phe7) with L-Ala brings about variable losses of affinity. All analogues maintain full intrinsic activity in the guinea pig ileum; [Ala10]-SP and [Ala11]-SP maintain more than 80% of intrinsic activity in the mesenteric vein, the other analogues being full agonists; moreover, [Ala7]-SP and [Ala 8]-SP show a weaker hypotensive potency than all other compounds. The effect of SP is not modified by an inhibitor of the converting enzyme (YS 980), but that of SP free acid is either potentiated (rabbit mesenteric vein, rat vas deferens) or not modified (rat blood pressure, guinea pig ileum).The findings presented in this paper are discussed in terms of structure–activity relationships. However, no clear indication has emerged as to the identity of the active group(s) or on a possible distinction between the molecular sequences or groups involved in binding or in stimulation of receptors by SP.

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