Loss of CarT affects the histamine, β-alanine, and carcinine contents <i>in vivo</i>.

<p>(A-C) Head histamine, β-alanine, and carcinine contents in the three genotypes indicated. (A-B) The <i>tan</i>^<i>1</i> and <i>cart</i>^<i>1</i> mutants had significantly less histamine and β-alanine than wild-type flies (<i>w</i>^<i>1118</i>). (C) The <i>tan</i>^<i>1</i> mutants had nearly three times as much carcinine as wild-type flies, and <i>cart</i>^<i>1</i> flies only showed a 35% increase in carcinine content. Error bars indicate SD; significant differences between mutant and wt flies were determined using unpaired t-tests (*p < 0.05; ***p < 0.001). (D) Model of the pathway for histamine recycling. After a light stimulus, the photoreceptor cells (PR) release histamine, synthesized by histidine decarboxylase (Hdc), into the synaptic cleft to activate histamine-gated chloride channels (HisClA) on postsynaptic neurons (LMC). The released histamine is quickly removed by an unknown histamine transporter in epithelial glial cells that express Ebony, and is then deactivated by conjugation to β-alanine. The histamine metabolite carcinine is then transported out of epithelial glial cells (Glia) by a second unknown transporter, and back to photoreceptors by means of the CarT transporter at the photoreceptor cell terminals, where carcinine is then hydrolyzed back into histamine by Tan ready to be pumped into synaptic vesicles in preparation for further release.