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At least 73 records · Page 4Linked to original sources
PubMed1978

Quantitative determination of ergot alkaloids in biological fluids by radioimmunoassay.

1 Cross-reactivity of ergot alkaloids with an antiserum produced against lysergic acid conjugated with human serum, albumin was utilized to develop a radioimmunoassay for ergotamine, dihydroergotamine, dihydroergotoxine, ergometrine and methylergometrine in biological fluids. The antisera showed no cross-reactivity with simpler indole structures. 2 A procedure for extraction and concentration of alkaloids in biological fluids was developed. 3 The assay is sensitive for 1.8 ng/ml ergotamine, 1.5 ng/ml dihydroergotamine, 2.2 ng/ml dihydroergotoxine, 0.7 ng/ml ergotmetrine and 0.5 ng/ml methylergometrine. 4 The assay is sufficiently sensitive to permit the measurement of urine and plasma ergot alkaloid levels and it is suitable for determination in cases where a known ergot alkaloid is used.

Cross Reactions↗
PubMed2006

Effects of ergot alkaloids on food preference and satiety in rabbits, as assessed with gene-knockout endophytes in perennial ryegrass (Lolium perenne).

Neotyphodium species are fungal endophytes best known for their protection of grass hosts and production of bioactive metabolites including ergot alkaloids. Perennial ryegrass-Neotyphodium sp. Lp1 symbiota that have altered ergot alkaloid profiles (resulting from knockouts in two different endophyte genes) were fed, along with controls, to rabbits to test the effects of ergot alkaloids on food preference and satiety. Interestingly, rabbits dramatically preferred plants that were endophyte-infected but free of ergot alkaloids over endophyte-free plants (P = 0.01). Accumulation of ergot alkaloids of the clavine class counteracted the added appeal of endophyte-infected plants. In satiety tests, consumption of ergovaline (the ultimate ergot pathway product in wild-type endophyte), but not of several other ergot alkaloids, during an initial meal had a negative effect on subsequent rabbit chow consumption (P < 0.05). The data indicate that clavines were sufficient to reduce the appeal of endophyte-infected grasses, whereas only ergovaline reduced appetite.

Animals↗
PubMedDate not supplied

[Use of polymerase chain reaction for searching for producers of ergot alkaloids from among microscopic fungi].

The potential of the polymerase chain reaction for the detection of ergot alkaloid producers among microscopic fungi of the genera Penicillium and Claviceps was evaluated. Twenty-three strains of various species of fungi with a previously studied capacity for alkaloid production were used. The internal fragment of the gene encoding 4-dimethylallyltryptophan synthase, the enzyme catalyzing the first step in the biosynthesis of ergot alkaloids, was amplified using degenerated primers. This approach revealed an about 1.2-kb specific DNA fragment in micromycetes synthesizing ergot alkaloids with complete tetracyclic ergoline system. Microorganisms that produce alkaloids with modified C or D ergoline rings, as well as alpha-cyclopiazonic acid, did not yield the PCR fragment of the expected size. This fragment was also not found in fungi incapable of ergot alkaloid production.

Alkyl and Aryl Transferases↗
PubMed1976

Ergot alkaloids as dopamine agonists: comparison in two rodent models.

A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protective effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic seizures was apomorphine greater than ergocornine greater than bromocryptine greater than ergometrine greater than LSD greater than methysergide greater than piribedil while that observed in the rotating mouse model was apomorphine greater than ergometrine greater than ergocornine greater than bromocryptine greater than piribedil. LSD caused only weak circling behaviour even when administered in high doses (greater than 1 mg/kg). Methysergide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed.

Acoustic Stimulation↗
PubMed1987

Interaction between some ergot alkaloids and the reactivity to dopamine of an identified neurone of Helix pomatia.

The effect of ergot alkaloids, some of them from the ergosine series, was tested on the response of an identified neurone of Helix pomatia to the application of dopamine (DA) which was membrane hyperpolarization (DA-I response). To evaluate the antagonistic potency of the ergot alkaloids, the dose-response relationship of the response to DA was established first in the absence and later in the presence of the tested compound. The sigmoidal dose-response curves obtained were used to determine the pA2 values of all the antagonists tested. Comparing them it was found that among the ergosines tested, the most potent was dihydroergosine, its pA2 value being (6.27) similar to the values obtained for dihydroergotoxine (6.66) and dihydroergotamine (6.36). The two other unhydrogenated compounds (ergosine and saccharinoergosine) had potencies of the same order as bromoergocryptine. The D-isomer (+) of the saccharino compound was the least potent, but it acted as a DA-receptor antagonists, as well as the dextroisomer of bromoergocryptine, bromoergocryptinine. By comparing the current-voltage relationship of the neurone in the presence and absence of the ergot alkaloids tested it was found that they had no non-specific effects on the membrane. The ergot alkaloids did not change the amplitude of depolarization of the neurone induced by gamma-aminobutyric acid (GABA) and acetylcholine (ACh).

Animals↗
PubMed1987

Dopamine receptor stimulating effects of chanoclavine analogues, tricyclic ergot alkaloids, in the brain.

The abilities of tricyclic ergot alkaloids, chanoclavine-I and its analogues, and bromocriptine to stimulate dopamine receptors in the brain were investigated. Receptor binding of 3H-spiperone has shown that bromocriptine exhibits clear affinity for this compound. The order of displacement potencies was bromocriptine much greater than ergometrine, KSU-1415 greater than chanoclavine-I, KSU-1118, KSU-1791. In the striatum of mice treated with an amino acid decarboxylase inhibitor, gamma-butyrolactone-induced DOPA accumulation was markedly inhibited by bromocriptine and KSU-1415, but not inhibited by chanoclavine-I. In mice with unilateral striatal 6-hydroxydopamine lesions, bromocriptine and KSU-1415 produced a long-lasting contralateral rotation that was suppressed by prior treatment with (+/-)-sulpiride. These results suggest that a tricyclic ergot alkaloid of the chanoclavine type stimulates D-2 receptors in the brain.

4-Butyrolactone↗
PubMed1978

Blockade of photically induced epilepsy by 'dopamine agonist' ergot alkaloids.

The effect of the intravenous administration of ergot alkaloids on epileptic responses to intermittent photic stimulation )IPS) has been studied in adolescent baboons, Papio papio, from Senegal. Ergocornine, 1--2 mg/kg, produced marked autonomic and behavioural effects, slowed the EEG, and abolished myoclonic responses to IPS for 30--90 min. Ergometrine, 1 mg/kg, activated the EEG and blocked the induction of myoclonic responses for 1--3 h. Bromocriptine, 0.5--4 mg/kg, did not consistently prevent myoclonic responses to IPS. After pretreatment with a subconvulsant dose of allylglycine (180--200 mg/kg), lysergic acid diethylamide, 0.1 mg/kg, retained the capacity to block myoclonic responses to IPS, and ergocornine 1 mg/kg reduced such responses. The convulsant effect of allylglycine was enhanced, however, so that prolonged seizure sequences began 19--96 min after ergocornine administration. The protective action of ergot alkaloids against epileptic responses induced by sensory stimulation is interpreted in terms of effects at several sites, including dopaminergic and serotoninergic synapses.

Allyl Compounds↗
PubMed2006

Mass spectral characterization of ergot alkaloids by electrospray ionization, hydrogen/deuterium exchange, and multiple stage mass spectrometry: Usefulness of precursor ion scan experiments.

Six ergot alkaloids belonging to the lysergic acid derivatives (ergonovine (EGN) and methysergide hydrogen maleinate (MHM)) and peptide-type derivatives (ergocristine (EGR), ergotamine (EGT), ergocornine (EGC) and alpha-ergokryptine (EGK)) were studied by positive electrospray tandem mass spectrometry. The fragmentation mechanisms of these compounds were studied by collision-induced dissociation (CID) using triple quadrupole and ion trap mass spectrometers, and the nature of the major product ions further confirmed by hydrogen/deuterium (H/D) exchange experiments. A common abundant product ion at m/z 223 was characteristic of the two classes of ergot alkaloids. Therefore, a precursor ion scan of m/z 223 that triggers information data acquisition (IDA) in combination with CID experiments was used to identify other potential ergot alkaloids. Using this approach, it was possible to confirm the presence of ergosine, another peptide-type ergot alkaloid, in a rye flour extract at trace levels.

Deuterium↗
PubMed2006

Post-genome research on the biosynthesis of ergot alkaloids.

Genome sequencing provides new opportunities and challenges for identifying genes for the biosynthesis of secondary metabolites. A putative biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid of the clavine type, was identified in the genome sequence of ASPERGILLUS FUMIGATUS by a bioinformatic approach. This cluster spans 22 kb of genomic DNA and comprises at least 11 open reading frames (ORFs). Seven of them are orthologous to genes from the biosynthetic gene cluster of ergot alkaloids in CLAVICEPS PURPUREA. Experimental evidence of the identified cluster was provided by heterologous expression and biochemical characterization of two ORFs, FgaPT1 and FgaPT2, in the cluster of A. FUMIGATUS, which show remarkable similarities to dimethylallyltryptophan synthase from C. PURPUREA and function as prenyltransferases. FgaPT2 converts L-tryptophan to dimethylallyltryptophan and thereby catalyzes the first step of ergot alkaloid biosynthesis, whilst FgaPT1 catalyzes the last step of the fumigaclavine C biosynthesis, i. e., the prenylation of fumigaclavine A at C-2 position of the indole nucleus. In addition to information obtained from the gene cluster of ergot alkaloids from C. PURPUREA, the identification of the biosynthetic gene cluster of fumigaclavine C in A. FUMIGATUS opens an alternative way to study the biosynthesis of ergot alkaloids in fungi.

Aspergillus fumigatus↗
PubMedDate not supplied

Characterization of the cytochrome P-450 gene family responsible for the N-dealkylation of the ergot alkaloid CQA 206-291 in humans.

The ergot alkaloid CQA 206-291 (CQA) was converted by human liver microsomes (n = 16) almost exclusively to the N-deethylated metabolite (I), as identified by the on-line coupling of liquid chromatography and mass spectroscopy. Metabolite I formation exhibited monophasic and linear enzyme kinetics (2.9-300 microM), and a 5.6-fold interindividual variability (7.2-40.2 nmol/mg/hr). Chemical inhibition experiments revealed that imidazole antimycotic agents (ketoconazole, miconazole, and clotrimazole) were potent inhibitors of this N-deethylation. Polymorphically metabolized substrates (sparteine and phenytoin), well-established cytochrome P-450 probe substrates (antipyrine and tolbutamide), and steroid hormones (estradiol and testosterone) were noninhibitory, indicating that their metabolism is catalyzed by forms of cytochrome P-450 that do not catalyze this route of CQA biotransformation. The ergot alkaloids--dihydroergotamine, bromocriptine, and SDZ 208-911--were competitive inhibitors of metabolite I formation, suggesting that these compounds are metabolized by similar enzymes. Cyclosporine A was a potent competitive inhibitor of CQA metabolism, providing initial evidence that formation of metabolite I was catalyzed by proteins of the CYP3 gene family. This was substantiated by the finding that CQA metabolism was completely inhibited by a polyclonal antibody directed against a pregnenolone 16 alpha-carbonitrile-inducible cytochrome P-450 of rat liver. The rate of CQA metabolism correlated significantly to the level of CYP3A4 expression, the rate of cyclosporine A metabolism to each of the primary metabolites (M-1, M-17, and M-21), and the rate of midazolam 4-hydroxylation. COS 1 cells transfected with human CYP3A4 and CYP3A5 provided direct evidence that these enzymes catalyze the metabolism of CQA.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites, Antibody↗
PubMed1980

Ergot alkaloids: interaction with presynaptic dopamine receptors in the neostriatum and olfactory tubercles.

Several ergot alkaloids, bromocriptine, ergocornine and lergotrile were shown to have potent agonist action at presynaptic dopamine receptors on striatal and mesolimbic nerve terminals in an in vivo model system. These agents blocked the increase in accumulation of striatal dihydroxyphenylalanine produced when impulse flow in the nigro-striatal dopamine system was inhibited by administration of gamma-butyrolactone. Administration of dopamine receptor blockers such as haloperidol prior to administration of the ergot alkaloids and apomorphine prevented the inhibitory effects of these agonists. However, when haloperidol was administered 50 min after the agonists although it completely blocked the effects of apomorphine it only partially antagonized the inhibitory effects of ergocornine and lergotrile and was ineffective in reversing the inhibitory effects of bromocriptine. Thus, this study in contrast to in vitro studies indicates that the ergot alkaloids do have potent effects on presynaptic dopamine nerve terminal receptors and that these agents, especially bromocriptine may interact non-competitively or irreversibly with presynaptic dopamine receptors.

4-Butyrolactone↗
PubMed1998

Effect of amino acid ergot alkaloids on glutamate transport via human glutamate transporter hGluT-1.

Effect of amino acid ergot alkaloids on glutamate transport via the human glutamate transporter (hGluT-1) was investigated using hGluT-HeLaS3 cells, which stably expressed high levels of hGluT-1. Ergotamine enhanced the glutamate uptake of hGluT-HeLaS3 cells in a concentration-dependent manner, increasing the initial velocity of glutamate uptake by 1.45 times at 10 microM. Other amino acid alkaloids, bromocriptine and dihydroergotamine, also augmented glutamate uptake, whereas amine alkaloids, ergonovine or lisuride did not influence glutamate uptake. The accelerating effect required a preincubation longer than 5 min. Kinetic studies on hGluT-1 revealed that ergot alkaloids decreased a Michaelis constant (Km) for glutamate with unchanged maximum velocity. The effect of bromocriptine was not mediated by dopamine D1 or D2 receptors, and was independent of its antioxidant action. Amino acid ergot alkaloids may serve as a prototype for agents that regulate glutamate transporters. These results may be useful in exploring new agents for neurological diseases associated with glutamatergic neurotoxicity.

ATP-Binding Cassette Transporters↗
PubMed2004

Fragmentation patterns of selected ergot alkaloids by electrospray ionization tandem quadrupole mass spectrometry.

Tall fescue toxicosis and other maladies in livestock result from the ingestion of vasoconstrictive ergot alkaloids produced by fungal endophytes associated symbiotically with the grass. In order to facilitate future analyses of grass extracts considered responsible for outbreak of related livestock diseases, we examined the electrospray ionization mass spectra of specific ergot alkaloids under conditions that permit protonation. Our purposes were both to record the spectra with interpretation of mechanisms of fragmentation and to derive commonalities that would allow the prediction of mass spectra of related compounds for which standards were not readily available. With [M + H](+) values in parentheses, water-insoluble lysergic acid peptide ergot derivatives ergovaline (m/z 534), ergotamine (m/z 582), ergocornine (m/z 562), ergocryptine (m/z 576) and ergocrystine (m/z 610) exhibited a consistent loss of water (-18 u) from the C-12' alpha-hydroxy functionality. Of this group, ergovaline and ergotamine generated an m/z 320 fragment deriving from cleavage of ring E amide and ether functions with retention of the peptide ring system methyl group. Ergocornine, ergocryptine and ergocrystine similarly formed an m/z 348 fragment with retention of isopropyl. These assignments were supported by the lack of similar fragments from the water-soluble ergot ergonovine, which lacks a peptide ring system. Clavine-type ergot alkaloids lysergic acid and lysergol lack any substituents beyond simple ones directly on the C-8 position and, similarly to ergonovine, lack significant fragments at m/z 268, 251 and 225 shared by the peptide ergot alkaloids.

Animal Feed↗
PubMed1996

Ergot alkaloid glycosides with immunomodulatory activities.

New glycosides derived from ergot alkaloids elymoclavine and DH-lysergol were synthesized by chemoenzymatic methods. beta-Glucosides were obtained either by chemical method or by transglycosylation (glycosidase from Aspergillus oryzae), lactosides were prepared by further extension of carbohydrate chain using beta-1,4-galactosyltransferase (bovine milk) and alpha-5-N-acetylneuraminyl-(2-->6)-beta-D-galactopyranosyl-(l-->4)-2- acetamido-2-deoxy-beta-D-glucopyranosyl-(1-->O)-elymoclavine was prepared using alpha-2,6-sialyltransferase (rat liver). Immunomodulatory activity of elymoclavine and 9,10-dihydrolysergol and their glycosylated derivatives on natural killer (NK) cell-mediated cytotoxicity of human resting and activated human peripheral blood mononuclear cells (PBMC) was investigated. Addition of ergot alkaloid glycosides to the mixtures of effector and target cells potentiated the PBMC cytotoxicity against both NK-sensitive and -resistant target cells. The glycoconjugates of elymoclavine enhanced cytotoxicity of PBMC against NK-resistant target cells. The glycoconjugates of DH-lysergol potentiated NK cytotoxicity of PBMC against NK-sensitive target cells.

Adjuvants, Immunologic↗
PubMed1999

Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.

A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway.

Alkyl and Aryl Transferases↗
PubMedDate not supplied

[The effect of some amino acids on the growth and biosynthesis of ergot alkaloids and quinocitrinins in the fungus Penicillium citrinum Thom 1910].

The effect of some amino acids, added to the medium either during inoculation or in the stationary growth phase, on the growth and biosynthesis of ergot alkaloids and quinocitrinins in the fungus Penicillium citrinum VKM FW-800 has been studied. Exogenously added amino acids were mostly utilized in primary metabolism. When added during inoculation, tryptophan and leucine virtually did not influence fungal growth and synthesis of the alkaloids, whereas the addition of isoleucine enhanced the biomass accumulation. When added in the stationary growth phase, tryptophan stimulated the synthesis of both ergot alkaloids and quinocitrinins. Leucine added in the stationary growth phase did not influence the synthesis of ergot alkaloids but inhibited the synthesis of quinocitrinins. Isoleucine inhibited the synthesis of both ergot alkaloids and quinocitrinins irrespective of the time of its addition to the medium.

Alkaloids↗
PubMed1999

Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes.

Ergocryptine is an ergot alkaloid that affects dopaminergic activity principally by interacting with D2-type receptors. In this study the ability of ergocryptine and several other ergot alkaloids to release [3H]dopamine from isolated nerve endings was demonstrated using in vitro superfusion of rat striatal synaptosomes. Ergocryptine, ergocristine, and bromocryptine produced an elevation in baseline dopamine release of approximately 400% with effective concentrations (EC50) of approximately 30 microM. Ergotamine, ergonovine, ergovaline, and ergocornine were devoid of activity. The time-course of the ergocryptine-stimulated release was relatively slow compared with amphetamine, nicotine, or K+-stimulated [3H]dopamine release; the maximal increase in release required a 5-min treatment. A number of receptor antagonists were examined for their ability to block ergocryptine-stimulated release. Of the dopaminergic, adrenergic, serotonergic, GABA-ergic, and cholinergic antagonists examined, only phentolamine produced a moderate attenuation in evoked release. Omission of Ca++ from the medium did not affect ergocryptine-evoked release. Following ergocryptine treatment, the synaptosomes were fully responsive to other stimulant. The results indicate that, in addition to interacting with dopamine receptors, several ergot alkaloids may produce dopaminergic effects by increasing the release of dopamine from central nerve endings. Several mechanisms to account for the evoked neurotransmitter release are discussed.

Animals↗