Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/81349
Full metadata record
DC FieldValueLanguage
dc.contributor.authorNeumann, Joachim-
dc.contributor.authorSeidler, Tom-
dc.contributor.authorFehse, Charlotte-
dc.contributor.authorMarušáková, Margaréta-
dc.contributor.authorHofmann, Britt-
dc.contributor.authorGergs, Ulrich-
dc.date.accessioned2022-04-05T07:05:20Z-
dc.date.available2022-04-05T07:05:20Z-
dc.date.issued2021-
dc.identifier.urihttps://opendata.uni-halle.de//handle/1981185920/83304-
dc.identifier.urihttp://dx.doi.org/10.25673/81349-
dc.description.abstractIt is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT4-receptors. Therefore, we studied transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes in the atrium and in the ventricle (5-HT4-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC50 = 6.0 ± 0.1; n = 7) from 5-HT4-TG, isolated spontaneously beating right atrial preparations (pEC50 = 6.1 ± 0.1; n = 7) from 5-HT4-TG, Langendorff perfused hearts from 5-HT4-TG, living 5-HT4-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT4-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT4-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT4-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT4-TG dextrally, resp., to higher concentrations: the pEC50 of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 μM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 μM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT4 receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT4-receptors.eng
dc.description.sponsorshipPublikationsfonds MLU-
dc.language.isoeng-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc616-
dc.titleCardiovascular effects of metoclopramide and domperidone on human 5-HT4-serotonin-receptors in transgenic mice and in human atrial preparationseng
dc.typeArticle-
local.versionTypepublishedVersion-
local.bibliographicCitation.journaltitleEuropean journal of pharmacology-
local.bibliographicCitation.volume901-
local.bibliographicCitation.publishernameElsevier-
local.bibliographicCitation.publisherplaceNew York, NY [u.a.]-
local.bibliographicCitation.doi10.1016/j.ejphar.2021.174074-
local.openaccesstrue-
local.accessrights.dnbfree-
Appears in Collections:Open Access Publikationen der MLU

Files in This Item:
File Description SizeFormat 
1-s2.0-S0014299921002272-main.pdf5.91 MBAdobe PDFThumbnail
View/Open