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.
Kidneys preserved for transplantation surgery sustain injuries caused by cold ischemia during storage. Additionally, kidneys harvested from non-heart-beating donors encounter the stress of warm ischemia. The aim of this study was to determine the specific cell types losing viability after warm and cold ischemia. In warm ischemia studies, the pedicles of left kidneys of Lewis rats were cross-clamped for up to 90 min. In cold ischemia studies, kidneys were flushed with cold University of Wisconsin solution and stored up to 48h at 0-1 degrees C. After warm or cold ischemia, kidneys were perfused via the renal arteries with Krebs-Henseleit bicarbonate (KHB) buffer at 37 degrees C, followed by trypan blue to label the nuclei of nonviable cells. Warm ischemia for 90 min caused renal failure and led to injury of proximal tubular cells, e.g., loss of brush borders, cast formation and trypan blue labeling. Cold ischemia for 48 h also caused renal failure but, unlike warm ischemia, caused trypan blue labeling of glomerular podocytes and peritubular endothelial cells. In warm ischemia-induced injury, electron microscopy showed shedding of microvilli and marked swelling of proximal tubular cells, microvilli and mitochondria. In cold ischemia-induced injury, podocytes were blebbed and swollen, and their pedicels were detached from the basement membrane, but disruption in proximal tubules was milder. In conclusion, warm ischemia triggers injury primarily to proximal tubular cells, whereas cold ischemia damages glomerular podocytes and peritubular endothelial cells in addition to proximal tubules.
Flushing renal explants with warm CRS before implantation diminishes cold ischemia-reperfusion injury and improves the function and survival of transplanted kidneys.
The photoreceptors of adult barnacles use histamine as their neurotransmitter and take up (3)H-histamine selectively from the extracellular medium. We assayed for the uptake of (3)H-histamine into the eyes of the free-swimming (nauplius) and settling (cyprid) larval stages of Balanus amphitrite. The extracellular space of nauplii proved permeable to dyes below about 800 molecular weight (MW), indicating that (3)H-histamine (MW 111) introduced into seawater would have access to internal structures. (3)H-Histamine was taken up into nauplii by a process with a K(D) of 0.32 microM. Uptake was antagonized by chlorpromazine, which also blocks uptake of (3)H-histamine into adult photoreceptors. In autoradiographs of serial sections of nauplii and cyprids incubated in (3)H-histamine, the ocelli and compound eyes were labeled; other structures in the animal were not. No eyes or other structures were labeled with (3)H-serotonin, a related amine whose transporter commonly transports histamine as well. These experiments show that a histamine-specific transporter similar to that found in the adult is expressed in all of the eyes of barnacle larvae. In the ocelli, where photoreceptors and pigment cells may be distinguished in the light microscope, label was unexpectedly concentrated far more over the pigment cells than over the photoreceptors.
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