Location and functions of Inebriated in the Drosophila eye.

Histamine (HA) is a neurotransmitter in arthropod photoreceptors. It is recycled via conjugation to beta-alanine to form beta-alanylhistamine (carcinine). Conjugation occurs in epithelial glia that surround photoreceptor terminals in the first optic neuropil, and carcinine (CA) is then transported back to photoreceptors and cleaved to liberate HA and beta-alanine. The gene Inebriated (Ine) encodes an Na+/Cl- dependent SLC6 family transporter translated as two protein isoforms, long (P1) and short (P2). Photoreceptors specifically express Ine-P2 whereas Ine-P1 is expressed in non-neuronal cells. Both ine(1) and ine(3) have significantly reduced head HA contents compared with wild type, and a smaller increase in head HA after drinking 1% CA. Similarly, uptake of 0.1% CAwas reduced in ine(1) and ine(3) mutant synaptosomes, but increased by 90% and 84% respectively for fractions incubated in 0.05% beta-Ala, compared with wild type. Screening potential substrates in Ine expressing Xenopus oocytes revealed very little response to carcinine and beta-Ala but increased conductance with glycine. Both ine(1) and ine(3) mutant responses in light-dark phototaxis did not differ from wild-type. Collectively our results suggest that Inebriated functions in an adjunct role as a transporter to the previously reported carcinine transporter CarT.