Abstract
The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells,
consistent with its tocolytic effect observed in patients. OT activates not only OT
receptors but also V1A receptors, two receptors with high receptor homology that are both expressed in the
myometrium and play a crucial role in myometrial contraction signaling. We aimed to
study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line
hTERT-C3, and cell lines expressing recombinant human OT and V1A receptors.
We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases
in hTERT-C3 myometrial cells. In additional assays performed with cells expressing
recombinant receptors, BPJ also inhibited OT and V1A receptor-mediated signals with a similar potency (IC50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in
hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency
(EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation
was corroborated by the antagonist potencies of atosiban and relcovaptan that we found.
However, using qPCR, we almost exclusively found expression of OT receptors suggesting
a pharmacological difference between recombinant OT receptors and native receptors
expressed in hTERT-C3 cells.
In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects
to other indications involving a disbalance in the vasopressinergic system.
Keywords
Bryophyllum pinnatum
- Crassulaceae - oxytocin - vasopressin - V
1A receptor - OT receptor - myometrium
