Selective, Activity-Dependent Uptake of Histamine into an Arthropod Photoreceptor

Abstract

The synapses made by many arthropod photoreceptors are disinhibitory and use histamine as their transmitter. Because decreases and not increases in the cleft concentration of transmitter constitute the important event at these synapses, a transporter to clear the cleft of histamine would seem particularly crucial to signal transfer. We report here that 3H-histamine is taken up selectively into barnacle photoreceptors by a Na+-dependent mechanism, presumably a transporter. Using light microscopic autoradiography, we observe heavy label over axons and presynaptic terminals of these neurons when they are stimulated during uptake. The radioactivity taken up was identified as 3H-histamine by thin layer chromatography; no metabolites were detected, even after 5 hr. Radiolabeled 5-hydroxytryptamine and GABA are not taken up by the photoreceptor. 3H-histamine uptake into photoreceptors is decreased markedly by an excess of unlabeled histamine and by chlorpromazine and phenoxybenzamine. Unexpectedly for uptake dependent on the NA+ gradient, photoreceptor terminals label more intensely in the light (when depolarized) than in the dark (when hyperpolarized). Glia label more strongly than photoreceptors in dark-incubated preparations. The presence of presynaptic uptake strengthens the evidence that histamine is the neurotransmitter of arthropod photoreceptors and provides a mechanism by which this synapse could recycle transmitter, control its steady-state cleft concentration, and clear it from the cleft in response to decreases in its release from the photoreceptors.

Ebony, a Novel Nonribosomal Peptide Synthetase for β-Alanine Conjugation with Biogenic Amines in Drosophila

“…Therefore, at the synapse where transmitter removal excites the postsynaptic cell by disinhibition, a mechanism of fast retraction of histamine from the synaptic cleft is essential. Interestingly, in illuminated barnacle photoreceptor preparations, [ 3 H]histamine was concentrated over the photoreceptor terminals, whereas after incubation in the dark, the label was found at the glia (33). This observation lends support to the concept that at darkening a fast clearance of transmitter out of the synaptic cleft would be achieved by transport of histamine into the surrounding glia where it could be trapped by Ebony via ␤-alanine binding.…”

“…The model requires that ␤-alanine is sufficiently loaded in the glia to prime Ebony for histamine capture and a biochemical pathway that allows the subsequent reuse of the withdrawn histamine in the photoreceptor. Although both histamine transport into photoreceptor as well as into glia has been reported previously (32,33), it remains to be investigated whether a mechanism exists that darkening and concomitant reduction of histamine release shifts uptake toward glia followed by immediate inactivation by ␤-alanine binding.…”

“…Therefore, it is plausible to assign to Ebony a function in histamine neurotransmitter metabolism at the photoreceptor synapse of the eye. Because histamine synthesis (31) as well as metabolic degradation (10) in the eye is relatively slow, the almost infinite transmitter supply must be maintained by a fast re-uptake system (32,33). Therefore, at the synapse where transmitter removal excites the postsynaptic cell by disinhibition, a mechanism of fast retraction of histamine from the synaptic cleft is essential.…”

Comparative sequence analysis and tissue localization of members of the SLC6 family of transporters in adultDrosophila melanogaster

“…Histamine is the neurotransmitter of Drosophila photoreceptors, and genetic evidence indicates that a mechanism to accumulate histamine into photoreceptors exists in Drosophila (Melzig et al, 1998), as it does in other species (Battelle et al, 1999;Stuart et al, 2002;Stuart et al, 1996). Flies lacking the enzyme that synthesizes histamine, histidine decarboxylase (HDC), are blind and have lost histamine immunolabelling in the optic lobe.…”

Genomic Structure of the Rat and Mouse Histamine N-Methyltransferase Gene

“…3). Although the existence of the membrane transporter specific for histamine has been suggested in the barnacle photoreceptors (4), it has not yet been identified in the mammalian body. In addition, DAO enzymatic activity has not been detected in the mammalian CNS (5), whereas HMT enzymatic activity and HMT-like immunoreactivity are present in the rat, mouse, and guinea pig brain (6).…”