Pharmacological studies of kinins in venous smooth muscles

1981 ◽  
Vol 59 (4) ◽  
pp. 371-379 ◽  
Author(s):  
P. Gaudreau ◽  
J. Barabé ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Guinea Pig ◽  
Jugular Vein ◽  
Biological Activities ◽  
Smooth Muscles ◽  
Response Curves ◽  
Kininase Ii ◽  
Structure Activity ◽  
Hexyl Ester ◽  
Pharmacological Studies ◽  
Specific Receptors

The myotropic effects of bradykinin (BK) and other kinins in two isolated veins, the rabbit jugular and the guinea pig anterior mesenteric, have been studied. The effects of degradation on the biological activities of these compounds and the receptor types mediating their myotropic effects have been determined.It has been found that contractions elicited by kinins in these veins result from direct actions on specific receptors. Both veins contain active kininase II (but not active carboxypeptidases A or B) which interferes with the measurement of the myotropic effects and can be blocked by 1-(D-3-mereapto-2-methyl-3-oxopropyl)-L-proline (SQ 14225). The slopes but not the maxima of the concentration–response curves of BK and other kinins measured in the presence of SQ 14225 are different from those recorded in its absence whereas no significant changes are observed in concentration–response curves obtained with the analogue [D-Phe8]-BK, which resists degradation by kininase II.BK is more potent than its fragment sequence des-Arg9-BK and the effects of kinins are antagonized by dihydrochlorprothixene and β-phenylalanine hexyl ester. These findings suggest that the rabbit jugular and the guinea pig anterior mesenteric veins contain receptors of the B2 type.The findings presented in this paper indicate that the rabbit jugular vein and the guinea pig anterior mesenteric vein are sensitive preparations for kinins and they can be useful for structure–activity studies of these peptides. A correct evaluation of the relative affinities of various kinins is, however, only possible by eliminating the interference of kininase II.

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.

scholarly journals Recent progress in the research of Angelica sinensis (Oliv.) Diels polysaccharides: extraction, purification, structure and bioactivities

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Chunyan Hou ◽  
Mingsong Yin ◽  
Ping Lan ◽  
Huiru Wang ◽  
Hui Nie ◽  
...  
Keyword(s):  
Functional Foods ◽  
Recent Progress ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Angelica Sinensis ◽  
Chinese Herbal ◽  
Structure Activity ◽  
Pharmacological Studies ◽  
Anti Inflammatory

AbstractThe root of Angelica sinensis (Oliv.) Diels, a well-known Chinese herbal medicine, has been used historically as hematopoietic and anti-inflammatory agents for thousands of years. Recent phytochemistry and pharmacological studies have proved that polysaccharides are one of the major active ingredients in A. sinensis. It has been demonstrated that ASPs (A. sinensis polysaccharides) had various important biological activities, such as hematopoietic, hepatoprotective, hypoglycemic, anti-inflammatory, antitumor, and antioxidant activities. The purpose of this present review is to appraise previous and current literatures on the extraction, purification, structural characterization and biological activities of ASPs. In addition, the structure–activity relationship will be further explored and discussed. We believe that this review will provide a useful bibliography for the investigation, production, and application of ASPs in functional foods and therapeutic agents. Moreover, this review also highlights the challenges of investigation and future considerations for holistic utilization.

The rabbit mesenteric vein: a specific bioassay for substance P

1978 ◽  
Vol 56 (4) ◽  
pp. 603-609 ◽  
Author(s):  
A. Bérubé ◽  
F. Marceau ◽  
J. N. Drouin ◽  
F. Rioux ◽  
D. Regoli
Keyword(s):  
Substance P ◽  
De Novo ◽  
Smooth Muscles ◽  
High Sensitivity ◽  
Mass Action ◽  
Response Curves ◽  
Mesenteric Vein ◽  
Mass Action Law ◽  
New Type ◽  
Specific Receptors

The anterior mesenteric vein of the rabbit responds to substance P with dose-dependent contractions and is among the vascular smooth muscles most sensitive to this peptide. In spite of its high sensitivity to numerous other agents, including angiotensin and bradykinin, the rabbit mesenteric vein can be made selective for substance P by the use of specific inhibitors that will prevent the myotropic effects of acetylcholine, catecholamines, histamine, 5-hydroxytryptamine, and of the two above-mentioned peptides, without modifying the contractions elicited by substance P. It appears that this peptide acts directly on specific receptors and not through the release of neurotransmitters. Interference by intramural prostaglandins is excluded because substance P is equally active on tissues pretreated with indomethacin or untreated.Dose–response curves obtained with substance P are close to the theoretical curves predicted by the mass action law. The rabbit mesenteric vein contains a new type of receptor for bradykinin, recently identified (REGOLI, D., MARCEAU, F., and BARABÉ, J. 1978. De novo formation of vascular receptors for bradykinin. Can. J. Physiol. Pharmacol. 56, in press.). The action of bradykinin on this receptor can be prevented with the use of specific and competitive inhibitors and, therefore, the mesenteric vein will distinguish between peptides of the kinins or of the substance P types.

Characterization of bradykinin receptors in peripheral organs

1991 ◽  
Vol 69 (7) ◽  
pp. 938-943 ◽  
Author(s):  
Nour-Eddine Rhaleb ◽  
Noureddine Rouissi ◽  
Guy Drapeau ◽  
Daniela Jukic ◽  
Domenico Regoli
Keyword(s):  
Urinary Bladder ◽  
Guinea Pig ◽  
Jugular Vein ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Arachidonic Acid Cascade ◽  
Receptor System ◽  
Kinin Receptors ◽  
Concentration Levels

Bradykinin (BK) and related kinins are potent stimulants of the rabbit jugular vein, the hamster urinary bladder, and the guinea pig trachea. The characterization of kinin receptors in these tissues was made with agonists and antagonists. Results obtained with agonists indicate that bradykinin and kallidin are much more active than des-Arg9-BK and suggest the presence of B2 receptors in the three organs. Some new agonists were also tested and the BK analogue, [Hyp3,Tyr(Me)8]BK, was found to be a potent and selective stimulant of the three preparations, with pD2 values of 8.56, 8.00, and 8.39, respectively, but inactive on the rabbit aorta (a B1-receptor system). Contractile effects of kinins in the rabbit jugular vein and hamster urinary bladder were reduced or eliminated by B2-receptor antagonists but at different concentration levels; e.g., acetyl-D-Arg[Hyp3,D-Phe7]BK showed pA2 values of 7.78 on the rabbit jugular vein but only 5.72 on hamster urinary bladder. This compound contracted the guinea-pig trachea and was found to be inactive as an antagonist on this preparation. Contractions of the hamster urinary bladder and the guinea-pig trachea in response to bradykinin were markedly reduced or eliminated by indomethacin and by BW 755C, while those of the rabbit jugular vein were not modified. The present findings indicate that the myotropic effect of kinins on the rabbit jugular vein depends on the activation of B2 receptors and suggest that B2 receptors are largely responsible also for the response of the hamster urinary bladder. B2 receptors and (or) a nonreceptor mechanism appear to be involved in the stimulant effects of the kinin agonists and some antagonists in the guinea-pig trachea.Key words: bradykinin, B2 receptors, agonists, antagonists, smooth muscles, arachidonic acid cascade, indomethacin, BW 755C.

A common mechanism links activities of butyrate in the colon

2017 ◽  
Author(s):  
Mohit S. Verma ◽  
Michael J. Fink ◽  
Gabriel L Salmon ◽  
Nadine Fornelos ◽  
Takahiro E. Ohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Histone Deacetylases ◽  
Biological Activities ◽  
Short Chain Fatty Acids ◽  
Common Mechanism ◽  
Epithelial Stem Cells ◽  
Degree Of Unsaturation ◽  
Structure Activity ◽  
Starting Point ◽  
New Compounds

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Synthesis, Characterization and Antiproliferative Activity Assessment of a Novel 1H-5-mercapto-1,2,4 Triazole Derivative

2017 ◽  
Vol 68 (4) ◽  
pp. 745-747 ◽  
Author(s):  
Marius Mioc ◽  
Sorin Avram ◽  
Vasile Bercean ◽  
Mihaela Balan Porcarasu ◽  
Codruta Soica ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Vascular Endothelial ◽  
Triazole Derivative ◽  
Activity Assessment ◽  
Wide Range ◽  
Specific Receptors ◽  
Endothelial Growth Factor ◽  
Selection Of

Angiogenesis plays an important function in tumor proliferation, one of the main angiogenic promoters being the vascular endothelial growth factor (VEGF) which activates specific receptors, particularly VEGFR-2. Thus, VEGFR-2 has become an essential therapeutic target in the development of new antitumor drugs. 1,2,4-triazoles show a wide range of biological activities, including antitumor effect, which was documented by numerous reports. In the current study the selection of 5-mercapto-1,2,4-triazole structure (1H-3-styryl-5-benzylidenehydrazino-carbonyl-methylsulfanil-1,2,4-triazole, Tz3a.7) was conducted based on molecular docking that emphasized it as suitable ligand for VEGFR-2 and EGFR1 receptors. Compound Tz3a.7 was synthesized and physicochemically and biologically evaluated thus revealing a moderate antiproliferative activity against breast cancer cell line MDA-MB-231.

Isothiocyanate Synthetic Analogs: Biological Activities, Structure-Activity Relationships and Synthetic Strategies

2014 ◽  
Vol 14 (12) ◽  
pp. 963-977 ◽  
Author(s):  
Andrea Milelli ◽  
Carmela Fimognari ◽  
Nicole Ticchi ◽  
Paolo Neviani ◽  
Anna Minarini ◽  
...  
Keyword(s):  
Biological Activities ◽  
Synthetic Analogs ◽  
Structure Activity Relationships ◽  
Structure Activity

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

Relationship between potency of L-isoprenaline and β-adrenoceptor density estimated in single cells from tracheal smooth muscles of guinea pigs of different ages

1992 ◽  
Vol 70 (4) ◽  
pp. 458-461 ◽  
Author(s):  
Issei Takayanagi ◽  
Mitsutoshi Satoh ◽  
Noriko Kokubu ◽  
Teruko Kato
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Dissociation Constants ◽  
Specific Binding ◽  
Single Cells ◽  
Regression Line ◽  
Smooth Muscles ◽  
Receptor Density ◽  
Age Related ◽  
Β Receptor

An age-related change in potency of L-isoprenaline in the presence of ascorbic acid, desmethylimipramine, corticosterone, pargyline, and phentolamine was obtained in tracheal strips from guinea pigs of differing ages between 6 and 40 weeks. The potency in the strips from 100-week-old guinea pigs did not significantly differ from that in strips from 40-week-old animals. Single cells were prepared from the tracheal muscles of 6-, 10-, 40-, and 100-week-old guinea pigs. The specific binding of [3H]dihydroalprenolol to the single cells was saturable. The dissociation constants of [3H]dihydroalprenolol were in good agreement with those of the membrane fractions from the guinea-pig tracheal muscles, and did not change with age. An excellent relationship between the potency of L-isoprenaline and the maximum binding of [3H]dihydroalprenolol estimated in the preparations from 6- to 40-week-old guinea pigs was found, suggesting that the increase in the potency of L-isoprenaline is due to the increase in the maximum binding or receptor density. The value in the preparations from 100-week-old guinea pigs deviated significantly from the regression line. This suggests the possibility that the decrease in potency in the strips from 100-week-old animals is due to a change in post β-receptor processes in responsiveness.Key words: guinea-pig trachea, single cells, β-receptor density, ageing, dissociation constant.

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