Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist and is clinically used to treat "off-states" in patients suffering from Parkinson's disease. Adverse effects of apomorphine treatment include severe emesis and nausea, and ulceration and pain at the injection site. We wanted to test whether sensory transient receptor potential (TRP) channels are a molecular target for apomorphine. Here, we show that rTRPV1, rTRPV2, rTRPV3, and mTRPV4, as well as hTRPM8, and rTRPM3, which are expressed in dorsal root ganglion neurons, are insensitive toward apomorphine treatment. This also applied to the cellular redox sensor hTRPM2. On the contrary, human TRPA1 could be concentration-dependently modulated by apomorphine. Whereas the addition of apomorphine in the low micromolar range produced an irreversible activation of the channel, application of higher concentrations caused a reversible voltage-dependent inhibition of heterologously expressed TRPA1 channels, resulting from a reduction of single-channel open times. In addition, we provide evidence that apomorphine also acts on endogenous TRPA1 in cultured dorsal root ganglion neurons from rats and in the enterochromaffin model cell line QGP-1, from which serotonin is released upon activation of TRPA1. Our study shows that human TRPA1 is a target for apomorphine, suggesting that an activation of TRPA1 might contribute to adverse side effects such as nausea and painful injections, which can occur during treatment with apomorphine.
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