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At least 19 recordsLinked to original sources
PubMed1999

Kallidin- and bradykinin-degrading pathways in human heart: degradation of kallidin by aminopeptidase M-like activity and bradykinin by neutral endopeptidase.

BACKGROUND: Since kinins kallidin (KD) and bradykinin (BK) appear to have cardioprotective effects ranging from improved hemodynamics to antiproliferative effects, inhibition of kinin-degrading enzymes should potentiate such effects. Indeed, it is believed that this mechanism is partly responsible for the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. In the heart, enzymes other than ACE may contribute to local degradation of kinins. The purpose of this study was to investigate which enzymes are responsible for the degradation of KD and BK in human heart tissue. METHODS AND RESULTS: Cardiac membranes were prepared from the left ventricles of normal (n=5) and failing (n=10) hearts. The patients had end-stage congestive heart failure as the result of coronary heart disease or idiopathic dilated cardiomyopathy. Heart tissue was incubated with KD or BK in the presence or absence of enzyme inhibitors. We found no difference in the enzymes responsible for kinin metabolism or their activities between normal and failing hearts. Thus KD was mostly converted into BK by the aminopeptidase M-like activity. When BK was used as substrate, it was converted into an inactive metabolite BK-(1-7) mostly (80% to 90%) by the neutral endopeptidase (NEP) activity, with ACE unexpectedly playing only a minor role. The low enzymatic activity of ACE in the cardiac membranes, compared with that of NEP, was not due to chronic ACE inhibitor therapy, because the cardiac ACE activities of patients, whether receiving ACE inhibitors or not, and of normal subjects were all equal. CONCLUSIONS: The present in vitro study shows that in human cardiac membranes, the most critical step in kinin metabolism, that is, inactivation of BK, appears to be mediated mostly by NEP. This observation suggests a role for NEP in the local control of BK concentration in heart tissue. Thus inhibition of cardiac NEP activity could be cardioprotective by elevating the local concentration of BK in the heart.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Kallidin effect on renal tubular function in meclofenamate- and vehicle-pretreated rats.

The effect of kallidin (lysyl-bradykinin) on the urinary recovery of sodium-22 was examined in anesthetized, volume-expanded rats. Sodium-22 was microinfused into the lumen of late proximal convoluted tubules with and without kallidin (100 pg/ml). Kallidin enhanced mean sodium-22 recovery from a control of 2.24 +/- 0.29% to 6.22 +/- 1.30% (delta = 3.98 +/- 1.31%, P less than 0.005). The urinary recovery of simultaneously microinfused inulin, mean blood pressure, urine flow, and the rate of tubular infusion were similar during control and kallidin microinfusions. Pretreatment of rats with meclofenamate (3.0 mg/kg) to inhibit renal prostaglandin synthesis blunted, but did not abolish, the effect of kallidin to promote sodium-22 recovery. The changes in sodium recovery induced by kallidin represent a 175 +/- 47% and a 58 +/- 11% increase from control values in vehicle- and meclofenamate-pretreated rats, respectively. The results indicate that kallidin, microinfused in high doses into the lumen of late proximal tubules, may lower sodium efflux in that nephron. Inhibition of prostaglandin synthesis reduced the tubular effect of kallidin, suggesting that enhanced prostaglandin synthesis may contribute to the natriuretic effects of kallidin. Alternatively, meclofenamate may directly oppose the tubular effect of kallidin.

Animals↗
PubMed2006

Kallidin-like peptide mediates the cardioprotective effect of the ACE inhibitor captopril against ischaemic reperfusion injury of rat heart.

1. The potential cardioprotective effect of ACE inhibitors has been attributed to the inhibition of bradykinin degradation. Recent data in rats documented a kallidin-like peptide, which mimics the cardioprotective effect of ischaemic preconditioning. This study investigates in isolated Langendorff rat heart the effect of the ACE inhibitor captopril, the role of bradykinin, kallidin-like peptide, and nitric oxide (NO). 2. The bradykinin level in the effluent of the control group was 14.6 pg ml(-1) and was not affected by captopril in the presence or absence of kinin B2-receptor antagonist, HOE140. 3. The kallidin-like peptide levels were approximately six-fold higher (89.8 pg ml(-1)) and increased significantly by treatment with captopril (144 pg ml(-1)), and simultaneous treatment with captopril and HOE140 (197 pg ml(-1)). 4. Following 30 min ischaemia in the control group, the creatine kinase activity increased from 0.4 to 53.4 U l(-1). In the captopril group and in the captopril+L-NAME group, the creatine kinase activity was significantly lower (18.5 and 22.8 U l(-1)). This beneficial effect of captopril was completely abolished by the kinin B2-receptor antagonist, HOE140, as well as by the kallidin antiserum. 5. Perfusion of the hearts with kallidin before the 30 min ischaemia, but not with bradykinin, yielded an approximately 50% reduction in creatine kinase activity after reperfusion. 6. Pretreatment with L-NAME alone and simultaneously with captopril, and with kallidin, respectively, suggests a kinin-independent action of NO before the 30 min ischaemia on coronary flow and a kinin-dependent action after ischaemia. 7. These data show that captopril increases kallidin-like peptide in the effluent. Kallidin-like peptide via kinin B2 receptor seems to be the physiological mediator of cardioprotective actions of captopril against ischaemic reperfusion injury. HOE140 as well as the kallidin antiserum abolished the cardioprotective effects of captopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Des-Arg(10)-kallidin engagement of the B1 receptor stimulates type I collagen synthesis via stabilization of connective tissue growth factor mRNA.

Expression of the kinin B1 receptor is up-regulated in chronic inflammatory and fibrotic disorders; however, little is known about its role in fibrogenesis. We examined human embryonic lung fibroblasts that constitutively express the B1 receptor and report that engagement of the B1 receptor by des-Arg(10)-kallidin stabilized connective tissue growth factor (CTGF) mRNA, stimulated an increase in alpha1(I) collagen mRNA, and stimulated type I collagen production. These events were not observed in B2 receptor-activated fibroblasts. In addition, B1 receptor activation by des-Arg(10)-kallidin induced a rise in cytosolic Ca(2+) that is consistent with B1 receptor pharmacology. Our results show that the des-Arg(10)-kallidin-stimulated increase in alpha1(I) collagen mRNA was time- and dose-dependent, with a peak response observed at 20 h with 100 nM des-Arg(10)-kallidin. The increase in CTGF mRNA was also time- and dose-dependent, with a peak response observed at 4 h with 100 nM des-Arg(10)-kallidin. The increase in CTGF mRNA was blocked by the B1 receptor antagonist des-Arg(10),Leu(9)-kallidin. Inhibition of protein synthesis by cycloheximide did not block the des-Arg(10)-kallidin-induced increase in CTGF mRNA. These results suggest that engagement of the kinin B1 receptor contributes to fibrogenesis through increased expression of CTGF.

Blotting, Northern↗
PubMed2005

Na+/Ca2+ exchanger activity modulates connective tissue growth factor mRNA expression in transforming growth factor beta1- and Des-Arg10-kallidin-stimulated myofibroblasts.

Transforming growth factor (TGF)-beta and des-Arg(10)-kallidin stimulate the expression of connective tissue growth factor (CTGF), a matrix signaling molecule that is frequently overexpressed in fibrotic disorders. Because the early signal transduction events regulating CTGF expression are unclear, we investigated the role of Ca(2+) homeostasis in CTGF mRNA expression in TGF-beta1- and des-Arg(10)-kallidin-stimulated human lung myofibroblasts. Activation of the kinin B1 receptor with des-Arg(10)-kallidin stimulated a rise in cytosolic Ca(2+) that was extracellular Na(+)-dependent and extracellular Ca(2+)-dependent. The des-Arg(10)-kallidin-stimulated increase of cytosolic Ca(2+) was blocked by KB-R7943, a specific inhibitor of Ca(2+) entry mode operation of the plasma membrane Na(+)/Ca(2+) exchanger. TGF-beta1 similarly stimulated a KB-R7943-sensitive increase of cytosolic Ca(2+) with kinetics distinct from the des-Arg(10)-kallidin-stimulated Ca(2+) response. We also found that KB-R7943 or 2',4'-dichlorobenzamil, an amiloride analog that inhibits the Na(+)/Ca(2+) exchanger activity, blocked the TGF-beta1- and des-Arg(10)-kallidin-stimulated increases of CTGF mRNA. Pretreatment with KB-R7943 also reduced the basal and TGF-beta1-stimulated levels of alpha1(I) collagen and alpha smooth muscle actin mRNAs. These data suggest that, in addition to regulating ion homeostasis, Na(+)/Ca(2+) exchanger acts as a signal transducer regulating CTGF, alpha1(I) collagen, and alpha smooth muscle actin expression. Consistent with a more widespread role for Na(+)/Ca(2+) exchanger in fibrogenesis, we also observed that KB-R7943 likewise blocked TGF-beta1-stimulated levels of CTGF mRNA in human microvascular endothelial and human osteoblast-like cells. We conclude that Ca(2+) entry mode operation of the Na(+)/Ca(2+) exchanger is required for des-Arg(10)-kallidin- and TGF-beta1-stimulated fibrogenesis and participates in the maintenance of the myofibroblast phenotype.

Blotting, Northern↗
PubMed1995

Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.

Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.

Adamantane↗
PubMed1990

Comparative airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects.

Bradykinin, kallidin (lys-bradykinin), and [des-Arg9]bradykinin are oligopeptides that may contribute as mediators in the pathogenesis of asthma by interacting with specific receptors designated B1 and B2. In this study, we have investigated the airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects. Changes in airway caliber were followed as maximum expiratory flow at 30% of the vital capacity (Vp30) and as forced expiratory volume in 1 s (FEV1). Only one of the six normal subjects responded to bradykinin at the maximum cumulative concentration (5.33 mg/ml). Neither kallidin nor [des-Arg9]bradykinin had any measurable bronchoconstrictor effect in the normal subjects whether airway caliber was measured as Vp30 or FEV1. In the 10 subjects with asthma, bradykinin and kallidin, but not [des-Arg9]bradykinin, produced a concentration-related fall in FEV1. The geometric mean provocation concentrations of inhaled agonist reducing FEV1 by 20% of baseline were 0.03, 0.08, and 0.44 mg/ml for bradykinin, kallidin, and histamine, respectively. Bronchoconstriction produced by bradykinin and kallidin was maximal within 3 to 5 min with recovery occurring over 30 to 45 min. Because bradykinin and kallidin are agonists of B2 receptors and [des-Arg9]bradykinin is an agonist for B1 receptors, these in vivo structure activity studies suggest that asthmatic, but not normal, airways are hyperresponsive to kinins when compared to histamine and that this potent bronchoconstrictor action is a specific pharmacologic effect compatible with the stimulation of B2 receptors or a variant of these.

Adult↗
PubMed1996

Comparison of the actions of kallidin and bradykinin in the skin of normal and psoriatic subjects.

With the recent development of selective drugs acting on the kinin system and the identification of a kallikrein-like enzyme from psoriatic blister fluid, there is now much interest in the possible role of kinins in psoriasis. We have examined the time-course of the inflammatory (weal and flare) responses to intradermal kallidin (lysbradykinin) and bradykinin in normal volunteers, and have compared the dose-response effect of these agents in normal volunteers and patients with psoriasis. Initially, normal subjects (n = 5) received coded intradermal injections of 50 microliters normal saline containing kallidin or bradykinin (0.1, 0.5, 1.0 and 5.0 micrograms). Weal volume, weal area and flare area were calculated at 5, 15, 30 and 60 min by measuring two perpendicular diameters and change in skinfold thickness. Weal and flare measurements were subsequently made at 15 and 5 min, respectively. Patients with psoriasis (n = 9) and normal subjects (n = 10) were given intradermal injections of kallidin (0.1 and 1.0 microgram) and bradykinin (0.1, 0.5 and 1.0 microgram) in clinically normal forearm skin, using histamine and normal saline as controls. The dose-response effects of kallidin on weal and flare responses in human skin were established in the study and compared with those of bradykinin. There was wide inter-individual variability for both agents and, although mean responses to the highest doses of kallidin and bradykinin were decreased in psoriatic skin, no significant differences were found between the psoriatic and normal group for kallidin, bradykinin or histamine. Hence, there do not appear to be any obvious altered vascular responses to kallidin or bradykinin in patients with psoriasis, despite the fact that kinins may be generated in psoriatic tissue.

Adult↗
PubMed1996

B2-kininergic action of linear and cyclic tryptophan6- and tyrosine6-kallidin.

This study was undertaken to determine the importance of the central aromatic moiety in the kallidin and cyclokallidin molecules, using the relaxation of the isolated duodenum of the rat. Replacement in kallidin of the central phenylalanine by tryptophan increased the potency from an EC50 of 3 x 10(-10)M to 2 x 10(-12)M. Replacement by tyrosine decreased the potency to an EC50 of 8 x 10(-8)M. In cyclo-kallidin (EC50: 10(-8)M) the potencies were decreased: cyclo-Trp6-kallidin showed an EC50 of 10(-6)M and cyclo-Tyr6-kallidin of 3 x 10(-7)M. The relaxation of the rat duodenum by linear and cyclic kinins was potentiated by the bradykinin potentiating peptide BPP5a and antagonized by the B2 antagonist HOE-140. At a concentration of 10(-9)M, HOE-140 significantly decreased the potencies of bradykinin and cyclo-kallidin, but not of the B1 agonist desArg9-bradykinin.

Animals↗
PubMed1990

Kallidin-induced stimulation of inositol phosphate production and prolactin release in rat anterior pituitary cells.

The effect of the kinin, kallidin (lysyl-bradykinin) on phosphoinositide metabolism and prolactin secretion was examined in male rat anterior pituitary cells in primary culture. Kallidin was found to stimulate both total inositol phosphate production and prolactin release. The stimulation of inositol phosphate was biphasic in nature, similar to that previously reported for bradykinin, although kallidin was approximately 10-fold more potent. Kallidin also stimulated prolactin secretion provoking a maximal stimulation of 193.0 +/- 11.1 (sem)% at 1 mumol/l. These findings suggest that kallidin-induced prolactin secretion may be mediated intracellularly by activation of phosphoinositide metabolism. The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release. The B1 agonist des-Arg9-bradykinin has previously been shown to have no effect on either parameter. As the effects of kinins on anterior pituitary cells do not appear to be mediated by either of the known kinin receptors, they may, therefore, act via a hitherto unrecognised kinin receptor.

Animals↗
PubMed1993

Cross-tachyphylactic airway response to inhaled bradykinin, kallidin and [desArg9]-bradykinin in asthmatic subjects.

Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1957

A comparative study of kinin, kallidin, and bradykinin.

Partially purified kinin, a polypeptide in wasp venom, has been found to be a potent smooth-muscle stimulating and hypotensive agent. Such a preparation was 10 to 100 times more effective than histamine in enhancing capillary permeability on intradermal injection, and 10 times more effective than acetylcholine in evoking pain on a cutaneous blister base. Some differences between the actions of salivary kallikrein and trypsin in releasing kallidin or bradykinin have been observed, and some modifications of previous methods of preparing crude kallidin and bradykinin are suggested. Kallidin and bradykinin are effective enhancers of capillary permeability in the guinea-pig and rabbit. Chemical and pharmacological tests failed to differentiate between kallidin and bradykinin which must be, therefore, closely similar compounds. The possible role of kallidin and bradykinin in physiological or pathological conditions is discussed.

Acetylcholine↗
PubMed1991

Kallidin stimulates prolactin secretion from individual rat anterior pituitary cells.

Kinins are localized within the adenohypophysis where they have been shown to stimulate the release of pituitary hormones. In the present study we have investigated the effect of [Lys]-bradykinin (kallidin) on prolactin secretion at the single cell level from cultured male rat anterior pituitary cells. This was assessed by use of a reverse haemolytic plaque assay which permits quantitative evaluation of the proportion of all pituitary cells which are secreting prolactin, and the amount of prolactin secreted per lactotroph (plaque area). The rate of plaque development was used as an index of the rate of hormone secretion in time-course studies. Kallidin induced a dose-dependent increase in both the percentage of plaque-forming cells and the median plaque area during the first 2 and 3 h of incubation respectively. The threshold concentration of kallidin was 10 nmol/l. After 4 h of kallidin stimulation there was no difference between treated and control monolayers with respect to median plaque area and the total secretion index. Although recruitment of additional cells into the secretory pool cannot be excluded, this seems unlikely since at 3 and 4 h little or no difference was observed in the number of plaque-forming cells. The data suggest that initially kallidin accelerated the rate of prolactin secretion primarily by inducing an increase in the number of cells secreting prolactin, and subsequently by increasing the amount of hormone secreted per lactotroph. The results presented here are consistent with the proposed role of the kallikrein-kinin system in the paracrine or autocrine control of prolactin release from the pituitary gland.

Animals↗
PubMed1991

Kallidin applied to the human nasal mucosa produces algesic response not blocked by capsaicin desensitization.

Various kinins (dissolved in 50 microliters) were applied to the nasal mucosa of healthy human volunteers to test the algesic and proinflammatory effects of these peptides in an intact human tissue. [des-Arg9]-bradykinin (0.5 mumol) was found to be inactive, while bradykinin (0.05-0.5 mumol) and especially kallidin (0.005-0.5 mumol) induced: (a) a mild painful sensation described as burning and pricking (latency 30 s, duration 3-5 min), (b) perception of pulsatility and obstruction in the nasal cavity (onset 1 min, duration 6-8 min). Substance P (0.5 mumol) and neurokinin A (0.5 mumol) produced slight obstruction and weak pulsatile sensation but not pain. Capsaicin (0.05 nmol) produced pain and secretion of fluid, but not pulsatile sensation. The effects of kallidin were not affected by repeated (to induce desensitization) applications of capsaicin (0.5 mumol). Likewise, ipratropium bromide (80 mg in 100 microliters) did not affect responses to kallidin. In an intact human tissue, kallidin produces various effects, including an algesic response, that are apparently independent from activation of B1 receptors and from desensitization of capsaicin-sensitive primary afferents.

Adult↗
PubMed2005

Rat tissue kallikrein releases a kallidin-like peptide from rat low-molecular-weight kininogen.

The kallikrein-kinin system is subdivided into the plasma and tissue-kallikrein-kinin system, with bradykinin (BK) and kallidin (KAL) (Lys(0)-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue-kallikrein. BK, but not KAL, has been detected in rats until now. One can explain this observation by the structural differences found in the sequence of rat high- and low-molecular kininogen containing an Arg-residue instead of a Lys-residue in front of the N-terminus of the BK sequence. Nevertheless, we were able to measure a kallidin-like peptide (KLP), in rat plasma and urine, using a specific KAL antiserum. In order to confirm our data, we isolated low-molecular-weight kininogen from rat plasma and incubated it with purified rat glandular kallikrein. The generated peptide was retained on a high-pressure liquid chromatography column and displaced by an excess of angiotensin I. The KLP-containing fraction was identified with the KLP radioimmunoassay. A specific ion signal with a mass to charge ratio (m/z) of 1216.73 was detected with matrix-assisted laser desorption/ionization mass spectrometry. As proposed earlier, the structure of this peptide is Arg(1)-KAL, instead of Lys(1)-KAL. The structural similarity between the Lys- and the Arg-residue explains the high crossreactivity (80%) of KLP with the specific KAL antibody. The incubation of KLP with angiotensin-converting enzyme yields two molecules with masses of 913.4 and 729.3 containing the sequence H-Arg-Arg-Pro-Pro-Gly-Phe-Ser-Pro-OH and H-Arg-Arg-Pro-Pro-Gly-Phe-OH. The enzymatic cleavage could be inhibited by captopril. The data suggest that in rats, as in other mammals, the tissue kallikrein-kinin system mediates its physiological effects via a kallidin-like peptide, which is Arg(1)-kallidin (Arg(0)-bradykinin).

Amino Acid Sequence↗
PubMed1991

Comparative nasal effects of bradykinin, kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers.

1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists kallidin and bradykinin both induced a dose-dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to kallidin and bradykinin between rhinitic and non-rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis.

Adult↗
PubMed2002

Contraction-related factors affect the concentration of a kallidin-like peptide in rat muscle tissue.

In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anaesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mM), adenosine (50 or 100 microM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a kallidin-like peptide. Also, the simultaneous perfusion with 100 microM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 microM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml(-1) insulin, induced an increase in the concentration of the kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.

Adenosine↗