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J Barabé

Publications and source records attributed to J Barabé.

32 records · Page 2Linked to original sources
PubMed1981

Pharmacological studies of kinins in venous smooth muscles.

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-mercapto-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 beta-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.

3-Mercaptopropionic Acid↗
PubMed1981

Structure-activity study of kinins in vascular smooth muscles.

To explore further relations between the chemical structure and the biological activities of kinins, a series of bradykinin fragments and analogues was prepared by the solid-phase method. Bradykinin and kallidin were also extended at the C- or the N-terminal end by the addition of one or more residues in order to evaluate the importance of peptide chain length and of additional positive charges at the N-terminal end for the biological activity. After purification by cation-exchange chromatography and gel filtration, the compounds were characterized by thin-layer chromatography, paper electrophoresis, elemental analyses, and amino acid analyses. All compounds were tested on three vascular preparations (the dog common carotid artery, the rabbit jugular vein, and the guinea pig anterior mesenteric vein) in order to measure their relative potencies as relaxant (on the dog common carotid artery) or as stimulant (the two veins) of vascular smooth muscles. The compounds were also tested on the cat terminal ileum and the rabbit aorta for comparison. The results reported in this paper indicate that all new analogues of bradykinin as well as some fragments and analogues described before by us and by other workers are full agonists in the three vascular preparations. No partial agonists or antagonists have been identified. The order of potency of the various kinin analogues is similar in the three vascular preparations and follows the same pattern as that found in the cat terminal ileum. It is therefore concluded that (a) the three vascular preparations utilized in the present experiment possess a B2 receptor type that appears to be similar to that of the cat terminal ileum and of the rat uterus described before and (b) receptors of the B2 type are able to mediate both the inhibitory and the excitatory actions of kinins in vascular smooth muscles.

Animals↗
PubMed1980

Kinin receptors in experimental inflammation.

The contractile response of the rat isolated urinary bladder to kinins is meated by receptors of the B1 and of the B2 types, as this preparation responds to des-Arg9-bradykinin (des-Arg9-BK), a fairly selective stimulant of receptor B1 and to [Tyr(Me)8]-BK, a potent agonist on receptor B2. Des-Arg10-[Leu9]-kallidin, a specific and competitive antagonist of the action of kinins on receptor B1, has been found to block the effect of des-Arg9-BK in concentrations similar to those required in the rabbit aorta; therefore, the B1 receptor of the rat urinary bladder is analogous to that of the rabbit vascular tissue. The response of the rat urinary bladder to des-Arg9-BK increases progressively from near null level during the incubation in vitro and can be abolished by cycloheximide; this suggests that receptor B1 of the rat urinary bladder is formed de novo. The inflammation of the bladder induced by intravesical injection of the detergent Triton X-100 enhances the initial response to des-Arg9-BK without modifying the response to other agents. The B1 receptor is formed in vivo in the rat urinary bladder submitted to the Triton X-100 treatment but not in the control untreated organ. The local de novo synthesis of B1 receptors for kinins that follows a noxious stimulus is proposed as a possible mechanism implicated in the chemical mediation of the inflammatory process.

Animals↗
PubMed1979

Cardiovascular actions of kinins in the rabbit.

The hypotensive action of bradykinin (BK) and congeners was measured in anesthetized rabbits by administering the peptides intravenously and intraarterially in order to evaluate their pulmonary inactivation. A systematic study of the distribution of receptors for BK in the cardiovascular system of the rabbit was approached: (a) by measuring the myotropic effects of several peptides related to BK in strips of large arteries and veins; (b) by recording the changes of tension and rate of isolated atria; and (c) by evaluating the changes of perfusion pressure in isolated hearts, kidneys, and ears. This investigation was extended to strips of aortae of various mammals and to isolated atria of guinea pigs, for comparison. Receptors for BK were classified into two main types, B1 and B2, using the order of potency of these agonists [Tyr(Me)8]-BK, BK, and [des-Arg9]-BK, and an antagonist, specific and competitive for the B1 receptors, the octapeptide [Leu-OMe8,des-Arg9]-BK. The results obtained in this study indicate that the complex cardiovascular effect of BK in vivo may result from direct actions on vascular smooth muscles, presumably mediated by at least two types of receptors, as well as from the release of endogenous prostaglandins. BK and congeners exert a direct action on vascular smooth muscle by stimulating specific receptors both of the B1 type (in the aorta, the large arteries, and the mesenteric vein) and of the B2 type (in the jugular vein); and these vascular tissues provide useful preparations for pharmacological studies of bradykinins. Isolated organs perfused through their main arteries with physiological medium respond to BK by an increase of perfusion pressure (vasoconstriction in isolated ears and kidneys) or by a decrease (vasodilation in the rabbit heart). The vascular effects of BK in the heart and the kidney depend in part on the release of endogenous prostaglandins and on the activation of receptors that appear to be of the B2 type. Like other endogenous hypotensive agents, BK appears to reduce the tonus of the peripheral vessels, while contracting large arteries and veins. The results obtained in vitro are discussed with respect to the hypotensive effect in vivo and to the role of kinins in inflammation and oedema.

Animals↗
PubMed1978

Synthesis of peptides by the solid-phase method. III. Bradykinin: fragments and analogs.

The natural sequence of bradykinin (BK) and 55 fragments or analogs of this peptide were perpared via the solid-phase method. The peptides were purified using ion-exchange (O-carboxymethyl(CM) and partition (Sephadex G-25) chromatography. The purity of each peptide was established by paper and thin-layer chromatography, paper electrophoresis, amino acid analysis, and biological assays. The compounds were tested in anesthetized rats (tested in vivo) and in two smooth-muscle preparations (rabbit aorta strip, cat ileum strip) in which BK produces contraction by stimulating specific receptors of different types. Some of the new peptides are interesting in that they either resist pulmonary inactivation, or are more potent than BK itself, or antagonize the myotropic effect of BK in rabbit aorta strips.

Animals↗
PubMed1978

De novo formation of vascular receptors for bradykinin.

Two different types of receptors for bradykinin have been found in isolated veins of the rabbit. The first receptor is a stable component of the smooth muscle membrane and it is found in the jugular vein, while the second is generated de novo during incubation in vitro and it is present in the mesenteric vein. Actinomycin D and cycloheximide block the generation of receptors in the mesenteric vein, without exerting any action either on receptors for other agonists (e.g. substance P) in the same tissue, or on the other receptor for bradykinin in the jugular vein.

Animals↗
PubMed1977

Conformational features of bradykinin. A circular dichroism study of the aromatic side-chains.

The circular dichroism (CD) of the peptide hormone bradykinin and its analogues, [Phe(H4)5]-bradykinin, [Phe(H4)8]bradykinin, [Phe(H4)5,8]bradykinin, [TyrOMe5]bradykinin, [TyrOMe8]bradykinin and [TyrOMe5.8]bradykinin, is described. The comparison of the CD spectra of these analogues with each other, recorded under a variety of conditions (pH, solvent, temperature), allows the monitoring of the behaviour of the aromatic side-chains (phenylalanine, tyrosine) and an estimation of their respective spectral contributions in both spectral regions (320-250 nm, 250-190 nm) with good precision. Conformational non-equivalence of the residues Phe-5 and Phe-8 together with some overall conformational features of bradykinin are thus established.

Bradykinin↗
PubMed1977

Does indomethacin antagonize the effects of peptides and other agents on the coronary circulation of rabbit isolated hearts.

The coronary vasodilator effects of substance P, bradykinin, eledoisin, adenosine, and nitroglycerin have been tested in rabbit isolated hearts perfused with physiological medium. It has been found that substance P is the most potent vasodilator and that the peptides are 10-100 times as active as adenosine and nitroglycerin. The effect of bradykinin is reduced by 50% in the presence of indomethacin (2.8-5 X 10(-6) M) while the actions of the other vasodilator are not influenced. At such concentrations, indomethacin is inactive on its own and blocks the effects of small and intermediate doses of arachidonic acid, the prostaglandin precursor. It suggested that edogenous prostaglandins do not play any major role in mediating the coronary vasodilation produced by several peptide and nonpeptide agents, but may account for about 50% of the effect of bradykinin.

Animals↗
PubMedDate not supplied

The cardiovascular response to epicardial application of neurotensin in guinea pigs.

Topical application of picomoles of neurotensin (NT) on the surface of the left ventricle (epicardial application) of anesthetized guinea pigs evoked dose-dependent pressor effects and tachycardia. The pressor response to epicardial NT was attenuated by pentolinium, a mixture of phentolamine and propranolol, or by guanethidine. However it was not affected by indomethacin, atropine or by a mixture of mepyramine and cimetidine. The tachycardia caused by epicardial NT was not modified by any of the aforementioned drugs. Both the pressor effects and tachycardia elicited by epicardial application of NT were markedly inhibited by chronic treatment of guinea pigs with capsaicin, and by topical application of lidocaine or tetrodotoxin to the surface of the left ventricle. Epicardial application of calcitonin gene-related peptide (CGRP), substance P (SP) or capsaicin also elicited tachycardia and either a decrease (CGRP and SP) or increase of blood pressure (capsaicin) in anesthetized guinea pigs. Epicardial application of NT, CGRP, or capsaicin in isolated, perfused hearts of guinea pigs also caused tachycardia. Together, these results suggest that the pressor responses to topical application of NT on the surface of the left ventricle in anesthetized guinea pigs are partially reflex in nature and likely to result from the stimulation by NT of cardiac sympathetic, capsaicin-sensitive, sensory nerve endings, whereas the tachycardia caused by epicardial NT appears to be due both to direct and indirect effects of NT on ventricular muscle cells. The possible participation of CGRP and/or SP in the chronotropic effect of NT applied on the epicardium, and their putative role as neurotransmitter of cardiac, capsaicin-sensitive, sensory neurons are discussed.

Angiotensin II↗
PubMedDate not supplied

Epicardial application of bradykinin elicits pressor effects and tachycardia in guinea pigs. Possible mechanisms.

Topical application of bradykinin (BK) to the surface of the left ventricle (epicardial application) of anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. The pressor effect of epicardial BK was reduced by prior systemic treatment of animals with pentolinium or a combination of phentolamine and propranolol, but it was not affected by acute bilateral vagotomy or systemic administration of atropine, indomethacin, naloxone or a combination of mepyramine and cimetidine. The tachycardia caused by epicardial BK was not affected by any of the aforementioned drugs or by section of the vagi. Both the pressor effect and tachycardia evoked by epicardial BK were abolished by prior epicardial application of lidocaine, a local anesthetic, or by chronic systemic capsaicin treatment. These results suggest that the pressor effect of epicardial BK is partially reflex in nature and likely to result from the stimulation by BK of cardiac sympathetic, capsaicin-sensitive primary afferents, whereas the tachycardia caused by epicardial BK could be mediated by an intracardiac release of (a) cardioaccelerating substance(s) from cardiac, capsaicin-sensitive sensory nerve fibers and/or terminals.

Animals↗