Introduction to the Pharmacology of Ergot Alkaloids and Related Compounds as a Basis of Their Therapeutic Application

Berde, B.; Stürmer, Ewa K.

doi:10.1007/978-3-642-66775-6_1

Cited by 97 publications

(79 citation statements)

References 65 publications

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“…Some EA show structural similarity to the neurotransmitters serotonin and dopamine and have affinity to the cognate receptors in the central nervous system (1,12). Therefore, EA have long been used for treatment of a variety of disorders of the central and peripheral nervous systems (22).…”

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confidence: 99%

Comparison of Ergot Alkaloid Biosynthesis Gene Clusters in Claviceps Species Indicates Loss of Late Pathway Steps in Evolution of C. fusiformis

Lorenz

Wilson

Machado

et al. 2007

Appl Environ Microbiol

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The grass parasites Claviceps purpurea and Claviceps fusiformis produce ergot alkaloids (EA) in planta and in submerged culture. Whereas EA synthesis (EAS) in C. purpurea proceeds via clavine intermediates to lysergic acid and the complex ergopeptines, C. fusiformis produces only agroclavine and elymoclavine. In C. purpurea the EAS gene (EAS) cluster includes dmaW (encoding the first pathway step), cloA (elymoclavine oxidation to lysergic acid), and the lpsA/lpsB genes (ergopeptine formation). We analyzed the corresponding C. fusiformis EAS cluster to investigate the evolutionary basis for chemotypic differences between the Claviceps species. Other than three peptide synthetase genes (lpsC and the tandem paralogues lpsA1 and lpsA2), homologues of all C. purpurea EAS genes were identified in C. fusiformis, including homologues of lpsB and cloA, which in C. purpurea encode enzymes for steps after clavine synthesis. Rearrangement of the cluster was evident around lpsB, which is truncated in C. fusiformis. This and several frameshift mutations render CflpsB a pseudogene (CflpsB ⌿ ). No obvious inactivating mutation was identified in CfcloA. All C. fusiformis EAS genes, including CflpsB ⌿ and CfcloA, were expressed in culture. Crosscomplementation analyses demonstrated that CfcloA and CflpsB ⌿ were expressed in C. purpurea but did not encode functional enzymes. In contrast, CpcloA catalyzed lysergic acid biosynthesis in C. fusiformis, indicating that C. fusiformis terminates its EAS pathway at elymoclavine because the cloA gene product is inactive. We propose that the C. fusiformis EAS cluster evolved from a more complete cluster by loss of some lps genes and by rearrangements and mutations inactivating lpsB and cloA.

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Comparison of Ergot Alkaloid Biosynthesis Gene Clusters in Claviceps Species Indicates Loss of Late Pathway Steps in Evolution of C. fusiformis

Lorenz

Wilson

Machado

et al. 2007

Appl Environ Microbiol

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“…Unfortunately, the majority of reports of ergot poisoning in animals have not related effects on animal performance (feed consumption, weight gain and feed to gain ratio) to the concentration of total alkaloids and to their individual alkaloid content (Lorenz 1979 (Young 1981a.) High-pressure liquid chromatography was used to determine the individual alkaloid composition (Young 1981b fFor further details on structure or properties of individual alkaloids see Berde and Sturmer (1978).…”

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Effect of Ergot From Different Sources and of Fractionated Ergot on the Performance of Growing Chicks

Rotter¹,

Marquardt²,

Young³

1985

Can. J. Anim. Sci.

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RorrEn, R. G., MenQUARDT, R. R. aNo YouNc, J. C. 1985. Effect of ergot from different sources and of fractionated ergot on the performance of growing chicks. Can. J. A series of experiments was conducted on growing chicks to compare the toxic effects of ergot from different sources and to partially fractionate the toxic component(s) in ergot. Changes in body weight gain, feed consumption relative to control birds and mortality were used as indicators of toxicity. Seven-day-old male Leghorn chicks were offered feed containing ground ergot from rye, wheat and triticale for a period of 7 days. The ergot samples were obtained from different locations in Canada and were added to the diets so that the concentration of total alkaloids was either 45 or 90 mg/kg. The relative weight gains for birds fed diets containing 45 and 90 mg/kg total alkaloids varied considerably, ranging from 49 to 65Vo and tiom l8 Io 42Va of controls, respectively. The degree of depression in relative performance was not uniform among the different ergot samples when their concentration in the diet was increased. In a fractionation study, most of the toxic activity in the ergot was concentrated in the alkaloid fraction, suggesting that most of the toxic components are alkaloid related. There was also some loss of the alkaloids and the corresponding potency of toxic factors during the isolation. It may be concluded that the total alkaloid content of an ergot sample can be used to predict the effects of ergot on chick performance. However, it is not a highly accurate prediction due to the variable content and variable effects ofthe individual alkaloids in a given sample and because most of the toxic activity of ergot is associated with the alkaloid fiaction. RESULTS Experiment IThe total alkaloid content of the ergot samples from different regions of Canada that were used in exp.

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“…1982) and interpreted according to the principles outlined by Snedecor and Cochran (1980 (Burfening 1973;Lorenz 1979 (Berde 1980). Some may act to increase and others decrease the rate of passage, and the net result could be observed as no effect.…”

Section: Discussionmentioning

confidence: 99%

Effect of dietary ergot on the mean transit time of digesta in the small intestine of sheep

Rotter¹,

Phillips²

1991

Can. J. Anim. Sci.

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Introduction to the Pharmacology of Ergot Alkaloids and Related Compounds as a Basis of Their Therapeutic Application

Cited by 97 publications

References 65 publications

Comparison of Ergot Alkaloid Biosynthesis Gene Clusters in Claviceps Species Indicates Loss of Late Pathway Steps in Evolution of C. fusiformis

Comparison of Ergot Alkaloid Biosynthesis Gene Clusters in Claviceps Species Indicates Loss of Late Pathway Steps in Evolution of C. fusiformis

Effect of Ergot From Different Sources and of Fractionated Ergot on the Performance of Growing Chicks

Effect of dietary ergot on the mean transit time of digesta in the small intestine of sheep

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