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The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Cryptotis parva).


ABSTRACT: Subtypes (1-4) of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the central and peripheral nervous systems, as well as the cells of smooth muscles in many organs. They mainly serve to regulate cellular excitability in these tissues. The HCN channel blocker ZD7288 has been shown to reduce apomorphine-induced conditioned taste aversion on saccharin preference in rats suggesting potential antinausea/antiemetic effects. Currently, in the least shew model of emesis we find that ZD7288 induces vomiting in a dose-dependent manner, with maximal efficacies of 100% at 1 mg/kg (i.p.) and 83.3% at 10 µg (i.c.v.). HCN channel subtype (1-4) expression was assessed using immunohistochemistry in the least shrew brainstem dorsal vagal complex (DVC) containin

SUBMITTER: Zhong W 

PROVIDER: S-EPMC8117105 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature