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At least 19 recordsLinked to original sources
PubMed1981

An alpha-adrenoceptor inhibitory action of kynuramine.

Kynuramine, an endogenously occurring amine, inhibited the vasoconstrictor responses to norepinephrine in the isolated perfused mesenteric arteries of rats and blocked the relaxation of rabbit intestinal smooth muscle by phenylephrine. Similarly, kynuramine reversed clonidine-induced inhibition of the cholinergic twitch response in the guinea pig ileum. These effects, seen with concentration ranging from 4 to 60 microgram/ml, are consistent with an alpha-adrenoceptor inhibitory action of kynuramine at both presynaptic and postsynaptic sites. Kynuramine itself, lacked intrinsic activity on alpha-adrenoceptors and showed a complete lack of affinity for beta-adrenoceptors in the rabbit intestine and guinea pig tracheal chain preparation. None of the effects of kynuramine could be attributed to the formation of 4-hydroxyquinoline, the deaminated metabolite of kynuramine. Additionally, no evidence was obtained for an action on muscarinic receptors or non-specific effects on vascular smooth muscle. However, a slight, transient stimulant action was evident on intestinal smooth muscle. It is concluded that kynuramine inhibits both presynaptic and postsynaptic alpha-adrenoceptors in vitro and it is conceivable that the compound might function as an endogenous inhibitor of alpha-adrenoceptors in vivo.

Adrenergic alpha-Antagonists↗
PubMed1983

Cardiovascular actions of kynuramine and 5-hydroxykynuramine in pithed rats.

Kynuramines occur endogenously in brain and peripheral tissues as metabolites of indoleamino acids and indolamines but little is known regarding their possible physiological and/or pharmacological activity. The present study has investigated the effects of kynuramine and 5-hydroxykynuramine on the cardiovascular system of pithed rats and attempted to correlate effects seen on adrenergic and serotonergic receptors with ligand binding experiments done in vitro using rat brain membranes. Kynuramine was found to release cardiac catecholamines and to act as a weak partial agonist on vascular alpha-adrenoceptors. Hydroxylation in the 5-position (5-hydroxykynuramine) did not alter cardiac potency but increased pressor activity 100-fold. Vasopressor responses to 5-hydroxykynuramine were mediated via a dual agonistic action on both postsynaptic alpha 2-adrenoceptors and vascular serotonin2 receptors. These findings were supported by ligand binding studies, in which both kynuramine and 5-hydroxykynuramine showed affinity for cortical [3H]spiroperidol and [3H]clonidine binding sites. Overall, the results show that kynuramines can exert peripheral (and possibly central) actions which may prove to be of physiological and/or pharmacological significance.

Adrenergic alpha-Agonists↗
PubMed1984

Cardiac norepinephrine releasing action of kynuramine, an endogenous diamine derived from L-tryptophan.

Kynuramine, an endogenous metabolite of L-tryptophan, was found to function as an indirectly acting sympathomimetic amine in rat atria in vitro. Kynuramine released tritium from atria preloaded with [3H]norepinephrine (NE), an effect which was blocked completely by pretreatment with reserpine or 6-hydroxydopamine. Release by kynuramine was calcium-independent and was potentiated by inhibition of monoamine oxidase but was only partially sensitive (50%) to inhibition by cocaine (10(-4)M). The ability of kynuramine to enter cardiac cells was demonstrated in whole atria by measuring its intracellular deamination rate by monoamine oxidase. Blockade of neuronal uptake (cocaine) and extraneuronal uptake (SKF 550) had no effect upon this measure. It is concluded that knyuramine releases cardiac NE, in part, by a cocaine-sensitive mechanism but that the process operating for the membrane transport of kynuramine in both neuronal and non-neuronal cells remains uncertain. The data are discussed in relation to the possible cardiac consequences of L-tryptophan ingestion in man.

Animals↗
PubMed1983

Blood pressure and heart rate effects of kynuramine in pithed rats.

Kynuramine increased heart rate and blood pressure in pithed rats. Heart rate responses were blocked by beta-adrenoceptor antagonists and reserpine pretreatment. Both of these treatments reduced the pressor responses to kynuramine. Remaining pressor activity was inhibited by phentolamine. The pressor responses to kynuramine were reversed to depressor responses during infusion of norepinephrine but not vasopressin. It is concluded that kynuramine releases cardiac catecholamines and acts as a partial agonist on vascular alpha-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1984

Kynuramine: high affinity for [3H]tryptamine binding sites.

Kynuramine, an endogenously occurring metabolite of L-tryptophan, was found to displace [3H]tryptamine from its high affinity binding sites in rat brain cortex with an inhibition constant (Ki) of 28 nM. Kynuramine exhibited structural specificity and considerable selectivity, compared with its affinity for serotonergic, adrenergic and benzodiazepine recognition sites. This novel finding opens-up the possibility that kynuramine may exert physiological actions via the putative tryptamine receptor.

Animals↗
PubMed1987

Interaction of 5-hydroxykynurenamine, L-kynurenine and kynuramine with multiple serotonin receptors in smooth muscle.

The enzymatic formation of kynurenine derivatives from tryptophan and the regulation of this metabolic pathway by both tryptophan concentrations and plasma cortisol concentrations have raised the possibility that the kynurenine derivatives, L-kynurenine, kynuramine and 5-hydroxykynurenamine (5-OH-kynurenamine) may be important as endogenous agonists or antagonists at serotonin (5-HT) receptors in smooth muscle. In fact, 5-OH-kynurenamine was an agonist at 5-HT2 receptors in the rat jugular vein and aorta, at 5-HT3 (neuronal "M") receptors in the guinea pig ileum and at 5-HT receptors in the rat stomach fundus. Maximal contractile responses to 5-OH-kynurenamine in these three smooth muscle preparations were similar to those produced by 5-HT, although 5-OH-kynurenamine was approximately 10- to 100-fold less potent than 5-HT as a contractile agonist. Using appropriate antagonists, LY53857 as a selective antagonist at 5-HT2 receptors, ICS 205-930 as a selective antagonist at 5-HT3 receptors and 1-(1-napthyl) piperazine as a potent antagonist in the rat stomach fundus, we documented further that the contractile responses to 5-OH-kynurenamine resulted from its interaction with 5-HT receptors in these tissues. Kynuramine did not contract either the rat jugular vein, aorta or the guinea pig ileum, although a contractile response did occur in the rat stomach fundus (maximal response approximately 70% of the maximal contractile response to 5-HT). High concentrations of kynuramine (10(-4) M) produced modest inhibition and reduction in maximal responses to 5-HT in the jugular vein, aorta and guinea pig ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Intraventricular administration of l-kynurenine and kynuramine facilitates lordosis in the female rat.

Intraventricular administration of the tryptophan metabolites l-kynurenine (2-32 micrograms) and kynuramine (0.064-8 micrograms) facilitated lordosis behavior in estrogen-primed ovariectomized rats. The facilitatory effects of these drugs were not attenuated by pretreatment with the progesterone antagonist RU 38486, indicating that the effects were not mediated by release of adrenal progesterone. It is suggested that l-kynurenine and kynuramine may serve a physiological role in the modulation of female sexual behavior.

Animals↗
PubMed1977

Kynuramine, a fluorescent substrate and probe of plasma amine oxidase.

The fluorescence substrate kynuramine was used as a probe of the catalytic site of plasma amine oxidase. Under anaerobic conditions, the binding of kynuramine causes several spectroscopic changes. The Stokes shift (deltav = 5326 cm-) associated with binding of the substrate to the enzyme can be attributed to nonpolar properties of the binding site, whereas the increase in emission anisotropy (A = 33) indicates rigid attachment of the substrate to the enzyme. The fluorescence enhancement that follows the binding of substrate was used to determine the association constant (Ka). The enzyme plasma amine oxidase binds only 1 molecule of substrate with a Ka = 1.8 X 10(5) M-1 under anaerobic conditions. The use of fluorescence substrates seems to offer the possibility of monitoring conformational changes occurring prior to the catalytic event.

Animals↗
PubMed1983

Localization of rat striatal monoamine oxidase activities towards dopamine, serotonin and kynuramine by gradient centrifugation and nigro-striatal lesions.

Subfractionation of the crude synaptosomal-mitochondrial fraction of rat striatum in a continuous sucrose gradient in a zonal rotor led to the following results. The distribution pattern of monoamine oxidase (MAO) activity towards dopamine (DA) was very similar to the pattern of MAO activity towards serotonin (5HT), but differed from the pattern of MAO activity towards kynuramine (KYN). As 5HT is specifically deaminated by MAO-A while KYN is a common MAO substrate, this supports earlier suggestions that in rat striatal preparations DA is deaminated preferentially by MAO-A. The patterns of the MAO activities towards DA and 5HT were clearly dissimilar, despite considerable overlap, to the patterns of tyrosine hydroxylase (TH) and DOPA decarboxylase (DD) activity, both marking the presence of striatal dopaminergic synaptosomes. The peak activities were separated and all patterns were symmetrical without showing a shoulder. This indicates that rat striatal MAO activity towards DA and 5HT is not specifically or for the greater part localized in dopaminergic terminals. We also investigated the effects of electrolytic and 6-hydroxydopamine lesions of the substantia nigra, both causing extensive degeneration of striatal dopaminergic terminals as appeared from the large decrease of striatal TH and DD activity. However, neither type of lesion induced a reduction of the MAO activity towards any of the substrates used. It is concluded that the amount of MAO activity towards DA and 5HT (probably MAO-A activity) present in dopaminergic terminals is very low compared with the total activity of this enzyme in rat striatal tissue.

Animals↗
PubMed1985

A sensitive fluorometric assay for serum monoamine oxidase with kynuramine as substrate.

The detailed procedure of a new sensitive fluorometric assay for human serum monoamine oxidase (MAO) with kynuramine as substrate is described. The data on its reproducibility, stability, correlation with another method, and serum MAO levels for 150 healthy subjects and 205 patients with various diseases, are presented to support the usefulness of this method. Since our method is much simpler and more sensitive than other methods conventionally used, we can recommend it for routine clinical investigation.

Heart Failure↗
PubMed2004

Neutrophils as a specific target for melatonin and kynuramines: effects on cytokine release.

A growing body of evidence suggests that the pineal hormone, melatonin, has immunomodulatory properties, although very little is known about its effect on leukocytes. Therefore, we aimed to investigate the effect of melatonin and its oxidation product N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) on cytokine production by neutrophils and peripheral blood mononuclear cells (PBMCs). AFMK (0.001-1 mM) inhibits the lipopolysaccharide (LPS)-mediated production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) more efficiently in neutrophils than PBMCs. Moreover, the inhibitory activity of AFMK is stronger than that of melatonin. Interestingly, monocytes efficiently oxidize melatonin to AFMK. We conclude that neutrophils are one of the main targets for melatonin and that at least part of the effects described for melatonin on immune cells may be due to its oxidation product, AFMK. We also consider that the oxidation of melatonin may be an important event in the cross-talking between neutrophils and monocytes.

Analysis of Variance↗
PubMed1984

Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: involvement of serotonin receptors and alpha 1-adrenoceptors.

Kynuramines are endogenously occurring diamines derived from tryptophan. In the present study, we have compared the pharmacological actions of 5-hydroxykynuramine (5-OH-K) with kynuramine and 5-hydroxytryptamine (5-HT) on vascular resistance changes and responsiveness to adrenergic stimuli in the isolated perfused rat kidney. 5-OH-K was found to mimic the actions of 5-HT in that it produced vasoconstriction, potentiation of alpha 1-adrenoceptor-mediated responses to norepinephrine (NE) and periarterial nerve stimulation, and displaced specific [3H]spiroperidol binding from rat cortical membranes. With regard to all parameters measured, 5-OH-K was about 15-times less active than 5-HT. Vascular responses to 5-OH-K and 5-HT were inhibited noncompetitively by ketanserin and cyproheptadine. Unlike 5-OH-K, kynuramine, failed to evoke vasoconstriction and inhibited vascular responses to NE via alpha 1-adrenoceptors. Thus, kynuramine lacks serotonin receptor agonist activity but possesses alpha 1-adrenoceptor blocking properties. In contrast, 5-OH-K potentiates NE and acts as a serotonin agonist. The present results raise the possibility that kynuramine and 5-OH-K might act as endogenous modulators of serotonergic and adrenergic mechanisms in the renal vascular bed.

Animals↗
PubMed1977

Observations on the monamine oxidase activity of rat vasa deferentia, major blood vessels and human saphenous vein.

Monoamine oxidase (MAO) activity was characterized using whole tissue homogenates and kynuramine as the substrate. In rat vasa deferentia, kynuramine deamination was differentially inhibited by clorgyline, less so by deprenyl and not at all by pargyline. These studies, and mixed substrate experiments with tryptamine, proved that kynuramine is a substrate for MAO types A and B. Experiments made with rat abdominal aorta and inferior vena cava disclosed clorgyline-sensitive and resistant MAO activity, the latter being inhibited by semicarbazide but not by deprenyl or pargyline. No semicarbazide-sensitive species of MAO was found in human saphenous vein which also differed from the rat vasculature in that the predominant MAO activity was of the B type. It is concluded that kynuramine is also a good substrate for clorgyline-resistant enzymes and that rat vasculature may be a poor model for predicting deaminating mechanisms in human venous tissue.

Adult↗