1,720,997 research outputs found
In vivo characterization of B-2 receptors mediating hypotension in anesthetized rabbits and guinea pigs
No full textWith the discovery of suitable pharmacologic tools
for B 2 receptor characterization, it has been demonstrated in vitro that the pharmacological spectrum of
this receptor type obtained in various organs (e.g.
intestine, vessels, urogenital tract) remains the same
within the species but may show marked differences
among species (e.g. the rabbit, the guinea pig) (Regoli et al., 1993; Regoli et al., 1994). Thus, orders of
potency of agonists in rabbit and guinea pig tissues
are opposite in that [Hyp3]BK is approximately 50-
100 times more potent than [AibT]BK in the rabbit
and inversely, the latter compound is 2-10 times
more active than [Hyp3]BK in the guinea pig. Furthermore, competitive antagonists, such as DArg[Hyp3,d-PheV,LeuS]BK and WIN 64338 (a nonpeptide compound), have also shown differences in
their ability to block bradykinin responses in these
two species while HOE 140, a non-competitive and
long-acting antagonist, shows equipotent activities
on both. Based on these results, we have suggested
that B 2 receptors may be pharmacologically subject
to interspecies variability. The present study was
designed to find out if results obtained in vitro can
be reproduced in vivo by measuring pharmacological
parameters (namely EDs0 for agonists and ICso for antagonists) on kinin-induced blood pressure changes
in the rabbit and the guinea pig
FR 173657: a new, potent, nonpeptide kinin B2 receptor antagonist. An in vitro study
No full textFR 173657, the first effective nonpeptide kinin B2 receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B2 receptors, with pA2 values ranging from 8.2 to 9.4. FR 173657 is a selective B2 receptor antagonist that does not interact with human, pig, or rabbit B1 receptors. The new compound is extremely specific for the kinin B2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B2 receptors, whereas on pig and guinea pig receptors, i...FR 173657, the first effective nonpeptide kinin B2 receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B2 receptors, with pA2 values ranging from 8.2 to 9.4 FR 173657 is a selective B2 receptor antagonist that does not interact with human, pig, or rabbit B1 receptors. The new compound is extremely specific for the kinin B2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B2 receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist
Kinin receptors in the diabetic mouse
No full textIt has been proposed that kinins are important inflammatory mediators involved in the pathogenesis of several diseases. In the present study, we attempted to determine the effects of kinins in a type I diabetic mouse model, using in vitro assays. Injection of streptozotocin (STZ) to the C57BL/Ks mdb mice causes an insulitis (inflammation of Langerhans islets) that leads to the diabetic condition. Ten days following the STZ treatment, the mice showed increased glycemia. We examined the effect of kinins and other agents (substance P, neurokinin A, acetylcholine) on the stomach fundus and urinary bladder of control and diabetic mice. Our results show that the sensitivity of the stomach fundus to bradykinin (BK) and desArg9BK (DBK), but not to other contractile agents, was substantially increased in the tissues of diabetic mice. The maximal contractions induced by BK and DBK were increased 1.5- to 2-fold in the stomachs from diabetic mice compared with those from normal mice. BK induced similar maximal contractions of urinary bladder strips from normal or STZ-treated mice, while DBK did not show any effect on this preparation. Interestingly, the apparent affinities of all agonists are similar in the two groups, normal and diabetic. These results suggest that B, and B, receptors are overexpressed in the stomach fundus but not in the urinary bladder of diabetic mice
FR 173657: a new, potent, nonpeptide kinin B2 receptor antagonist. An in vitro study
No full textFR 173657, the first effective nonpeptide kinin B2 receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B2 receptors, with pA2 values ranging from 8.2 to 9.4 FR 173657 is a selective B2 receptor antagonist that does not interact with human, pig, or rabbit B1 receptors. The new compound is extremely specific for the kinin B2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B2 receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist
B1 and B2 kinin receptors in various species
No full textThe characteristic features of kinin B1 and B2 receptors are analyzed. Emphasis is placed on the pharmacologic profiles of B1 and B2 functional sites by the use of naturally-occurring kinins, some selective agonists, as well as peptide and non-peptide antagonists. Species differences are indicated, particularly between human, rabbit and mouse B1 receptors and also between human, rabbit and guinea pig B2 receptors. Extensive use has been made of the non-peptide B2 receptor antagonist, WIN-64338 (which is active in the guinea pig and inactive in the other species) and FR-173657 which shows high affinity in human, rabbit, mouse, pig and guinea pig B2 receptors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Antagonistic effects of FR173657 on human, pig, rabbit, and guinea pig kinin receptors: an in vitro study
No full textThe pharmacodynamic features of the new nonpeptide kinin B2 receptor antagonist FR 173657 were evaluated on pig, rabbit, guinea pig, and human native kinin B2 receptors. FR 173657 exerted high antagonistic activity in all preparations examined. In particular, it acts as a competitive antagonist in the rabbit jugular vein (pA2 8.9) and in the human umbilical vein (pA2 8.2) but as a noncompetitive antagonist in the pig coronary artery (pKB 9.2) and in the guinea pig ileum (pKB 9.2) stimulated with the selective B2 receptor agonist bradykinin (BK). In contrast, FR 173657 failed to antagonize the biological effects of the selective B1 receptor agonist LysdesArg9BK in the pig renal vein, rabbit aorta, and human umbilical vein, three kinin B1 receptor systems. Moreover, this compound was inactive against the effects induced by noradrenaline, 5-hydroxytryptamine, endothelin-1, angiotensin II, substance P, acetylcholine, and histamine in the B2 receptor preparations. Taken together, these results demonstrate that FR 173657 is the first potent nonpeptide B2 receptor antagonist with high affinity, selectivity, and specificity for kinin B2 receptors of different species, including man
Bradykinin receptors and receptor ligands (with special emphasis on vascular receptors)
No full textBradykinin and receptor ligand
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