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At least 19 recordsLinked to original sources
PubMed1977

The effects of bradykinin and the bradykinin potentiating peptide BPP5a on the electrical and mechanical responses of the guinea-pig taenia coli.

1 By means of the double sucrose-gap technique, the effects of bradykinin and the bradykinin potentiating peptide BPP(5a) were compared on the guinea-pig taenia coli under a number of experimental conditions.2 In normal Krebs solution the response to bradykinin was mostly a slight stimulation, characterized by a depolarization, an increase in spontaneous spike activity and a contraction. If BPP(5a) caused any effect at all, it was stimulation of the spike activity but without depolarization. Since the effect of bradykinin was little affected by an increase in dose, a potentiating effect of BPP(5a) could not be determined.3 Spontaneous spikes with a 5 to 7 s rhythm and prepotentials at their base were inhibited by bradykinin, whereas they were stimulated by BPP(5a).4 Oscillatory potentials (slow waves) induced by a calcium and magnesium-free medium were also suppressed by bradykinin and stimulated by BPP(5a). This effect of bradykinin was accompanied by a depolarization and a decrease in membrane resistance, phenomena not found after administration of BPP(5a).5 The amplitude of spontaneous spikes induced by potassium-depolarization was suppressed by bradykinin, even though the membrane resistance and potential had been decreased. BPP(5a) produced either no effect or a small stimulatory effect without influencing the membrane resistance.6 Reduction of the calcium concentration to 0.25 mM enhanced the stimulatory responses to both bradykinin and BPP(5a), especially the spike activity and depolarization. In this case the membrane resistance was increased by bradykinin as well as BPP(5a). These effects, especially those of BPP(5a), were inhibited by reduction of the sodium concentration to 15.5 mM. Reduction of the chloride concentration to 9.7 mM decreased rather than increased the stimulatory effects of both bradykinin and BPP(5a). Under these conditions bradykinin did not decrease the membrane resistance.7 Bradykinin can have both inhibitory and stimulatory effects on the taenia coli whereas BPP(5a) has only a stimulatory effect. Since under certain conditions both responses to bradykinin are accompanied by a sodium-dependent depolarization and decrease in membrane resistance, not influenced by lanthanum to any extent, it is suggested that bradykinin induces an increase in sodium conductance of the membrane. Under all the conditions investigated, except in low calcium, BPP(5a) did not affect the membrane potential and resistance. Thus, the underlying cause of its stimulatory effect is probably different from that of bradykinin.

Animals↗
PubMed1977

Pulmonary metabolism of bradykinin analogues and the contribution of angiotensin converting enzyme to bradykinin inactivation in isolated lungs.

1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of both analogues on guinea-pig ileum was potentiated (2.5-3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4-5 fold). 4 Like bradykinin, the 8-homo Phe analogue was extensively inactivated (greater than 90%) in a single passage through the pulmonary circulation of guinea-pig or rat isolated lungs and this inactivation was prevented by pre-treatment of the lungs with BPP9a. 5 The 7-homo Pro analogue was inactivated to a lesser degree in guinea-pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a. 6 It is concluded that the 8-homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7-homo Pro analogue is not a substrate. 7 There is about four times as much dipeptidylcarboxypeptidase activity in guinea-pig isolated lungs as there is in rat isolated lungs.

Animals↗
PubMed1979

Conformational features of bradykinin. A circular dichroism study of some peptide fragments and structural analogues of bradykinin.

The vasoactive hormone bradykinin, its N-and C-terminal fragments and some structural analogues were studied by Circular Dichroism. Conformational features of the peptide can be detected by comparative analysis of the various CD spectra recorded as a function of aqueous pH, solvent and temperature. It is shown that the two biologically essential arginine residues (Arg1 and Arg9) are important for the specific folded bradykinin conformation. Differences between bradykinin, its fragments and analogues become clearly established in conformational terms, and are discussed in relation to the biological activity of these peptides.

Bradykinin↗
PubMedDate not supplied

[Inflammation and host resistance against bacteria. I.--Increased resistance against Listeria monocytogenes and Salmonella typhimurium in mice, following their treatment with bradykinin, kallidin and methionyl-lysyl-bradykinin (author's transl)].

Mice pretreated with kinins are more resistant to a lethal challenge of Listeria monocytogenes. The multiplication of Listeria is decreased in the liver and spleen and the blood clearance of Salmonella typhi-murium is increased.

Animals↗
PubMedDate not supplied

The synthesis of bradykinin-azoprotein and its effectivity.

Some authors succeded in binding the bradykinin in form of a haptene by an azo-bridge to the human gammaglobulin as a vehicle. In this way, the bradykinin has been supplemented to a complete antigen. The bradykinin as a strongly vasoactive substance causes--after a local intradermal injection--an intensive circumscribed increase of the permeability of the capillaries. If such animals receive an intravenous or intracardiac injection of a 1% Evans blue solution, there is a strong blue colouring in the place where the bradykinin has been applied. The guinea pigs and the rabbits which had been immunized by bradykinin-azo-protein showed a significant decrease in the local accumulation of the Evans blue-solution,, which must be attributed to the immunologic neutralization of the intradermally injected bradykinin by an anti-bradykinin-antibody. The intradermally injected bradykinin is neutralized by the bradykinin-antibody. The intravenous or intracardiac injection of bradykinin causes a strong bronchoconstriction in the guinea pig. In those animals which have been pretreated with bradykinin-azo-protein, either there was no asthmatic dyspnoea at all or a decrease of the bronchial reaction would be found. This result very probably is also caused by the production and the activity of anti-bradykinin antibodies.

Alpha-Globulins↗
PubMed1979

Immunological and biological activities of fragments and analogs of bradykinin.

Using a number of analogs and fragments of a short-chain peptide bradykinin, a series of experiments have been carried out to assess the effect of modifications to the basic structure of the parent molecule on its myotropic and immunoreactive properties. Binding kinetics of both an antibody raised against the authentic nonapeptide and its specific biological receptor found in the guinea pig ileum were used to study these alteration effects. Peptide derivatives of bradykinin with an extension at the N-terminal (Lys- and Met-Lys-bradykinin) cross-react with the antibody raised to bradykinin 59 and 70% respectively. On the other hand, internal fragments with intact C-termini (2-9 and 3-9 bradykinin) react with this same antibody to an extent of 250 and 875% respectively, indicating that they are more potent antigens than the vasopressor molecule itself. Other internal fragments, as well as 9-substituted analogs effectively and not interact. These results indicated that the C terminal arginine of bradykinin is indeed essential in the binding mechanism with its antibody. This in turn illustrates the role of the carrier ovalbumin in the development of antiserum to the ovalbumin-toluene-diisocyanate-bradykinin complex. The physiological experiments with the guinea pig bioassay preparations lead to similar conclusions. Most internal fragments of bradykinin are devoid of activity, whereas N-terminal fragments (2-9, 3-9, and 5-9 bradykinin) have retained some activity again indicating a need for an intact arginine residue at the C-terminus of the molecule. Any modification in position 9 results in severe impairment of biological activity. Thus, the C-terminal residue of bradykinin must be conserved in order that the molecule may retain its immunological and physiological activities. Any extensions, deletions, or modifications of this site will severely retard these functions.

Amino Acid Sequence↗
PubMed1979

Bradykinin-induced renal hemodynamic alterations: renin and prostaglandin relationships.

The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal hyperemia is only partially dependent on enhanced prostaglandin release, the increase in renin secretion by bradykinin infusion after prostaglandin synthetase inhibition is consistent with a bradykinin and renin interaction, and the lack of a sustained hyperemia after bradykinin is related to increased renin-angiotensin system activity.

Angiotensin II↗
PubMed1979

[On the mode of action of bradykinin on smooth muscle (author's transl)].

At extremely low concentrations, in the picomole and the nanomole range, bradykinin produces contraction and relaxation of smooth muscle in the gastrointestinal and the urogenital tract. At the target organ, bradykinin interacts with discriminator proteins of the plasma membranes and triggers, via changes in certain membrane functions, its biological response:--The binding to the discriminator makes specific conformative and constitutional demands on the nonapeptide. The binding results from an angular conformation which exists in the solution. The complete sequence is responsible for this specific conformation. Consequently, the biological activity of partial sequences is low. The conformational analysis of analogues used in studies on the mechanism of action showed but slight differences from bradykinin. The interaction of these analogues with the discriminator protein is disturbed to a varying extent by modifications at positions 1, 5, 8 and 9 in the side chains. The affinity for the discriminator is affected, dependently on the respective configuration, by substitution on the beta-C atom in the two phenylalanine residues.--Bradykinin is not only bound to, but also degraded at, the plasma membranes of the rat uterus and duodenum. The bradykinin-degrading enzyme has been characterized as a kininase II with the aid of various inhibitors. The conformative and configurative prerequisites decisive for enzymatic degradation are others than those decisive for binding to the discriminator.--The changes in the activities of the membrane-bound adenylate and guanylate cyclases (produced by the bradykinin-discriminator complex) that take place at the rat duodenum and uterus in the presence of extracellular calcium ions contrast with each other: At the duodenum, the ratio between these two cyclic nucleotides is changed in favour of adenylate cyclase; and at the uterus, in favour of guanylate cyclase; Substances which increase or decrease the cAMP level may also potentiate or inhibit the relaxation of the duodenum. These bradykinin-induced changes in enzyme activity must be considered in connection with other effectors, e.g. prostaglandins and calcium ions.--The calcium-ion-dependence of the effect of bradykinin on the guinea-pig ileum and the rat uterus indicates the importance of these ions as additional second messengers. Bradykinin stimulates the influx of calcium ions into the ileum; it is ineffective if no extracellular calcium ions into the ileum; it is ineffective if no extracellular calcium ions are available. It seems that intracellular and membranal calcium is mobilized in the uterus, which is evidenced by results from experiments with EGTA on the isolated organ and by the release of calcium from plasma membranes after application of bradykinin. It is assumed that the observed changes in membrane functions are induced by the peptide-discriminator complex simultaneously and not in the form of a causal chain.

Animals↗
PubMed1977

The mechanism of action of two bradykinin-potentiating peptides on isolated smooth muscle.

Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings.

Animals↗
PubMed1979

The effects of captopril (SQ 14,225) on bradykinin-induced bronchoconstriction in the anesthetized guinea pig.

The effect of captopril (SQ 14,225) a potent inhibitor of angiotensin converting enzyme (ACE: kininase II) on the bronchoconstrictor response to bradykinin was studied in the anesthetized guinea pig. The i.v. administration of captopril caused a profound long lasting hypotension without affecting pulmonary resistance or dynamic compliance. Similarly, the i.v. administration of bradykinin caused small increases in pulmonary resistance and decreases in dynamic compliance which were not altered by the administration of captopril. However, after beta-receptor blockade with propranolol, bradykinin-induced changes in resistance and compliance were enhanced; additional captopril administration further potentiated the bradykinin effects. The prostaglandin synthetase inhibitor indomethacin antagonized the bradykinin-induced bronchoconstriction in beta-blocked animals and its potentiation by captopril. In the isolated perfused guinea pig lung, bradykinin caused a dose dependent release of a prostaglandin-like substance which was significantly increased by captopril and antagonized by indomethacin. These results suggest that bradykinin causes a prostaglandin-mediated bronchoconstriction. Captopril, a potent inhibitor of ACE, prevents the degradation of bradykinin thus potentiating the bradykinin-induced bronchoconstriction, an effect observed in intact animals only in the absence of pulmonary beta-receptor activation.

Airway Resistance↗
PubMed1979

Central and peripheral effects of bradykinin and prostaglandin E2 on blood pressure in conscious rats.

Bradykinin or prostaglandin E2 (PGE2), when injected intravenously, decreased blood pressure of conscious rats in a dose-dependent manner, while intracerebroventricular injections of bradykinin or PGE2 caused a dose-dependent increase in blood pressure. SQ 14,225, an inhibitor of angiotensin converting enzyme, potentiated the central pressor or peripheral depressor effect of bradykinin. Indomethacin, an inhibitor of prostaglandin synthesis, almost completely inhibited the central pressor effect of bradykinin when injected intraventricularly. Indomenthacin, when injected intravenously, failed to inhibit the peripheral depressor effect of bradykinin, whereas it significantly attenuated the peripheral depressor effect of bradykinin when the angiotensin converting enzyme was inhibited with SQ 14,225. These results suggest that the central pressor effect of bradykinin is mainly mediated by the synthesis of prostaglandins in the central nervous system, while only a small fraction of peripheral depressor effect of bradykinin is, at least in conscious rats, mediated by the synthesis of prostaglandins in the systemic circulation.

Animals↗
PubMed1979

On the contribution of prostaglandin-like substances to the action of bradykinin on intestinal motility and blood flow in canine jejunal loop in situ.

Blood flow and motility were studied in a canine jejunal loop in situ with intact innervation. Bradykinin was administered into a side branch of the supplying artery and indomethacin was infused intravenously 1 h before experiments. In the control group without indomethacin infusion, bradykinin 1-10 nmol/l gradually increased blood flow without significantly altering motility. Higher concentrations of bradykinin (20-100 nmol/l) augmented rhythmic contractions of the intestine. Phasic blood flow decreased during contraction and increased after relaxation, and mean blood flow increased. Bradykinin (0.2-1.0 mumol/l) caused tonic intestinal contractions. Blood flow initially increased but was soon impeded in proportion to the amplitude and duration of the tonic contractions. With intestinal muscle relaxation, blood flow increased to values markedly higher than control. In the group pretreated with indomethacin, blood flow did not increase after bradykinin administration. However, administration of PGE2 produced significant increase in flow, similar to that observed after bradykinin. Acetylcholine or isoprenaline also markedly increased blood flow. Increased intestinal motility caused by bradykinin mechanically impeded blood flow through the intestine, thus masking its direct vasodilating action. The action of bradykinin on the intestinal vascular bed is probably mediated or modulated by endogenous prostaglandin-like substances.

Acetylcholine↗
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↗
PubMed1975

Effect of bradykinin on transepithelial transfer of sodium and water in vitro.

Mucosal sodium and water transfer were measured in everted sacs of rat jejunum. 2. Bradykinin (7.86 X 10(-12)M), when present in both mucosal and serosal solutions, produced a biphasic effect on mucosal sodium and water transfer. When basal transfer was low a stimulation was observed whereas an inhibition of transfer was observed when basal transfer was high. Bradykinin at concentrations of 7-86 X 10(-11) and 7-86 X 10(-13) M produced qualitatively similar effects. 3. Inhibition of transfer was observed whether bradykinin was present in the mucosal, serosal or both solutions. Stimulation of transfer was observed only when bradykinin was present in the serosal solution. 4. Theophylline (1 mM), alone inhibited water transfer at high and intermediate levels of basal transfer, and significantly potentiated the inhibitory effect of bradykinin (7-86 X 10(-12)M) on water transfer at intermediate levels of control transfer. 5. Cyclic AMP (1 mM) inhibited water transfer when basal transfer was high. Dibutyryl cyclic AMP (1 mM) inhibited water transfer at all levels of basal transfer. Dibutyryl cyclic AMP (1 mM) and bradykinin (7-86 X 10(-12)M) together produced a significantly greater inhibition of water transfer than either agent alone, at intermediate basal transfer. 6. It was observed that the action of bradykinin upon sodium and water transfer consists of two different and opposing effects. It is possible that the inhibitory effect of bradykinin upon water transfer is related to increased cyclic AMP activity.

Animals↗
PubMed1978

Effects of locally and systemically infused bradykinin on transvascular fluid and protein transfer in the canine forelimb.

Local intra-arterial infusions of bradykinin into canine forelimbs perfused either naturally or at constant inflow markedly increase skin lymph protein concentration promoting edema formation. However, prolonged systemic infusions of this agent either intravenously or into the left ventricular chamber, in blood concentrations calculated to exceed those that produce massive protein and fluid efflux on local administration, causes only minimal increases in lymph protein concentration, and in naturally perfused forelimbs promotes extravascular fluid reabsorption rather than net fluid filtration. Local infusions of bradykinin fail to alter aortic pressure whereas systemic infusions produce a profound but transient decrease in this variable. Moreover, the local intra-arterial infusion of bradykinin into forelimbs perfused at constant inflow fails to increase skin lymph protein concentration after 60 minutes of systemic hypotension. In contrast to bradykinin alone, the simultaneous infusion of bradykinin and norepinephrine or bradykinin and isoproterenol fails to increase skin lymph protein concentration. The antagonism of the bradykinin protein efflux by both norepinephrine and isoproterenol can be prevented by prior treatment with propranolol. These data suggest that the liberation of catecholamines may account, in part, for the minimal increases in forelimb protein efflux during systemic infusions of bradykinin relative to that produced by local intra-arterial infusions of this agent.

Animals↗
PubMed1979

Production of antibodies against bradykinin.

High-titer antibodies against bradykinin were raised in rabbits. 2 different conjugates of bradykinin were used for immunization: bradykinin coupled to human serum albumin via 1,5-difluoro-2,4-dinitrobenzene and bradykinin coupled to edestin via 1-ethyl-3(3-dimethyl-aminopropyl)-carbodiimide. The sensitivity of the radioimmunoassay method is in the range of 1-50 pg of bradykinin. Cross-reaction of anti-bradykinin antisera occurred with kallidin and met-lys-bradykinin.

Animals↗
PubMed1978

Effects of aspirin and morphine on the release of a bradykinin-like substance into the subcutaneous perfusate of the rat paw.

The effects of aspirin and morphine on the release of bradykinin-like substance into the substaneous perfusate following various noxious stimuli were investigated in rat paw preparation. Subcutaneous perfusion was performed with saline or with saline containing o-phenanthroline or soy bean trypsin inhibitor at a rate of 3--4 drops/min. Ten drops per fraction were assayed for bradykinin activity. Pressure on the instep, application of heat to the foot and stimulation of the sciatic nerve were employed as noxious stimuli. Aspirin (200 mg/kg i.p.) inhibited the release of bradykinin due to heat, pressure and sciatic nerve stimulation, while morphine (5 mg/kg i.m.) inhibited only the release of bradykinin due to sciatic nerve stimulation. Results suggest that analgesics, such as aspirin and morphine, have a depressant action on pain by inhibiting the release of bradykinin locally. They also suggest that aspirin inhibits the release of bradykinin regardless of the type of noxious stimuli, while morphine inhibits the release of bradykinin which is mediated by neural mechanisms.

Animals↗