Volatile General Anesthetics Reveal a Neurobiological Role for the White and Brown Genes of Drosophila Melanogaster

Molecular and cellular evidence argues that a heterodimer between two ABC transporters, the White protein and the Brown protein, is responsible for pumping guanine into pigment-synthesizing cells of the fruit fly, Drosophila melanogaster. Previous studies have not detected White or Brown outside pigment-synthesizing cells nor have behavioral effects of null mutants been reported, other than those that are visually dependent. Nevertheless, we show here that exposure to the volatile general anesthetic (VGA) enflurane reveals a difference in neuromuscular performance between wild-type flies and those that carry a null allele in either the white or brown gene. Specifically, in a test of climbing ability, w1118 or bw1 flies are much less affected by enflurane than are congenic controls. Altered anesthetic sensitivity is still observed when visual cues are reduced or eliminated, arguing that white and brown contribute to neural function outside the eye. This hypothesis is supported by the detection of white message in heads of flies that are genetically altered so as to lack pigment-producing cells. The w1118 or bw1 mutations also alter the response to a second VGA, halothane, albeit somewhat differently. Under some conditions, the combination of w1118 with another mutation that affects anesthesia leads to a drastically altered phenotype. We consider several ways by which diminished transport of guanine could influence neural function and anesthetic sensitivity.