There are five muscarinic receptor subtypes expressed in the human heart. The main subtype is the M 2 -muscarinic receptor. We hypothesized that overexpression of the M 2 -muscarinic receptor should augment any contractile effects that are M 2 -muscarinic receptor–mediated. Therefore, we generated a transgenic mouse with overexpression of the human M 2 -muscarinic receptor under the control of the heart-specific α-myosin heavy...

Glucose-dependent insulinotropic polypeptide formerly called gastrin inhibitory peptide (GIP), a peptide composed of 42 amino acids, is formed in duodenal and jejunal cells. GIP acts via GIP receptors (GIPR). GIPR can stimulate adenylyl cyclases (AC) and increase intracellular cyclic adenosine-3´,5´-monophosphate (cAMP) levels. The physiological role of GIPR in the human heart is not fully understood. Thence, force of contract...

This research documents the paleoenvironmental evolution of Eighteen Mile Swamp on North Stradbroke Island (Minjerribah), Australia, from oscillating coastal lagoon into stable freshwater swamp over the last ca. 1600 years. We analyzed multiple sediment cores via physical description, acid sulfate soil assays, particle size analysis, diatom and pollen assemblages, photosynthetic pigment content, and Itrax XRF spectrometry, alo...

Cantharidin and sodium fluoride inhibit the activity of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) and increase the force of contraction in human atrial preparations. R-phenylisopropyl adenosine (R-PIA) acts as an agonist at A 1 -adenosine receptors. R-PIA exerts a negative inotropic effect on human atria. The effect of R-PIA—and its various manifestations—are currently explained as a function of the inhibitio...

Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D 1 -dopamine receptors (D 1 -TG). In D 1 -TG, first we noted that dopam...

MR33317 was synthesized as an acetylcholinesterase-inhibitor and an agonist at brain 5-HT 4 -receptors. MR33317 might be used to treat Morbus Alzheimer. This therapeutic action of MR33317 might be based on MR33317´s dual synergistic activity. We tested the hypothesis that MR33317 also stimulates 5-HT 4 -receptors in the heart. MR33317 (starting at 10 nM) increased force of contraction and beating rate in isolated atrial prepar...

The Cenozoic topographic development of the Himalaya‐Tibet orogen (HTO) substantially affected the paleoenvironment and biodiversity patterns of High Asia. However, concepts on the evolution and paleoenvironmental history of the HTO differ massively in timing, elevational increase and sequence of surface uplift of the different elements of the orogen. Using target enrichment of a large set of transcriptome‐derived markers, anc...

Dopamine can exert effects in the mammalian heart via five different dopamine receptors. There is controversy whether dopamine receptors increase contractility in the human heart. Therefore, we have generated mice that overexpress the human D 1 -dopamine receptor in the heart (D 1 -TG) and hypothesized that dopamine increases force of contraction and beating rate compared to wild-type mice (WT). In D 1 -TG hearts, we ascertain...

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed , Embase , and Web of Scienc...

Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atrial appendage (RAA) preparations. RAA were obtained during bypass surgery performed on human patients. These trabeculae were mounted...

Calsequestrin (CSQ2) is the main Ca 2+ -binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4–5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(−/−)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiography, in adult mice, the basal left ventricular ejection fraction and the spon...