3.4 Experimental section
3.4.2 Pharmacological methods .1 Materials
3.4.2.5 Histamine H 2 R assay on the isolated spontaneously beating guinea pig right atrium 4
Hearts were rapidly removed from guinea pigs used for studies on the ileum (see above).
The right atrium was quickly dissected and set up isometrically in Krebs-Henseleit solution under a diastolic resting force of 5 mN in a jacketed 20 mL organ bath of 32.5 °C as previously described.59 The bath fluid (composition [mM]: NaCl 118.1, KCl 4.7, CaCl21.8, MgSO41.64, KH2PO41.2, NaHCO325.0, glucose 5.0, sodium pyruvate 2.0) was gassed with 95% O2 – 5% CO2and additionally contained (RS)-propranolol (0.3 μM) and mepyramine (1 μM). Experiments were started after 30 min of continuous washing and an additional equilibration period of 15 min. Antagonists: Two successive concentration-frequency curves to histamine (0.1 – 30 μM) were established, the first in the absence and the second in the presence of the compound under study (incubation time 30 min). Agonists: Two successive concentration-frequency curves were established, the first to histamine (0.1 – 30 μM) and the second for the agonist under study. Furthermore, the sensitivity to 30 μM cimetidine was routinely checked at the end of each H2Ragonist concentration-effect curve established in the absence of an H2R antagonist, and a significant reduction of frequency was always observed after 15 – 30 min.
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