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Clonidine stimulates force of contraction via histamine H2 receptors in the human atrium
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Clonidine stimulates force of contraction via histamine H2 receptors in the human atrium
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Journal Article
Clonidine stimulates force of contraction via histamine H2 receptors in the human atrium
2024
Overview
Clonidine has various clinical effects mediated by agonism of α
1
- or α
2
-adrenoceptors and the blocking of hyperpolarization-activated-nucleotide-gated pacemaker channels (HCN). It is unknown whether clonidine can also stimulate human cardiac histamine H
2
receptors (hH
2
Rs). We used isolated electrically stimulated left and spontaneously beating right atrial preparations from mice overexpressing the hH
2
R specifically in the heart (H
2
-TG), and spontaneously beating right atrial preparations of guinea pigs for comparison. Moreover, we studied isolated electrically stimulated muscle strips from the human right atrium. Clonidine (1, 3, and 10 µM) increased force of contraction in isolated left atrial preparations from H
2
-TG mice. In contrast, clonidine reduced the spontaneous beating rate in right atrial preparations from H
2
-TG. Clonidine raised the beating rate in guinea pig right atrial preparations. Clonidine failed to increase the force of contraction but reduced beating rate in wild-type litter mate mice (WT). In WT, histamine failed to increase the force of contraction in left atrial preparations and beating rate in right atrial preparations. Clonidine (10 µM) increased the force of contraction in isolated human right atrial preparations. The positive inotropic effect in the human atrium was attenuated by cimetidine (10 µM). Clonidine increased the beating rate of the isolated spontaneously beating guinea pig right atrium and acted as a H
2
R partial agonist. Furthermore, clonidine showed binding to the guinea pig H
2
R (100 µM) using HEK cells in a recombinant expression system (p
K
i
< 4.5) but hardly to the human H
2
R. These data suggest that clonidine can functionally activate cardiac human H
2
R.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
