Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt

Abstract

The effects of chronic dietary sodium chloride (NaCl) consumption on renal function and brain dopamine receptors were studied in adult, male normotensive rats. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited significant increases in plasma aldosterone, chloride and changes in urinary electrolyte excretion. In contrast, rats maintained on the high NaCl (8%) diet for 4 weeks demonstrated significant increases in urine volume and urinary sodium, chloride and dopamine excretions and water intake. Rats fed the high NaCl diet displayed a 42-59% decrease (p < 0.001-0.05) in D1 binding in the nucleus accumbens (NA), olfactory tubercle (OT) and the striatum (STM), without any effects on D2 binding in these brain regions. Rats maintained on the low NaCl diet also demonstrated decreased D1 binding in the ventral (24%, p < 0.02) and lateral (29%, p < 0.01) STM, but not in the OT, NA, entopeduncular nucleus and substantia nigra. Rats fed low or high NaCl diets exhibited a 35-180% increase (p < 0.01-0.05) in D2 binding in several mid-brain areas (e.g. hypothalamus, thalamus and hippocampus) and hindbrain regions (e.g. superior colliculus and nucleus tractus solitarius) without affecting the D1 binding. These data indicate that chronic modification of dietary salt intake profoundly affects the renal handling of sodium/water excretion and leads to selective up- and/or down-regulation of DA receptor subtypes in different areas of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular Hypotensive DP-Class Prostaglandin Receptor Affinities Determined by Quantitative Autoradiography on Human Eye Sections

“…After equilibration of the tissues at Ϫ17°C for 2-4 hours, 20 m sagittal sections were cut using a Brights freezing microtome (Brights Instruments Co. Ltd., Huntingdon, UK) and collected on gelatinized glass microscope slides, as previously described. [18][19][20][21] For the receptor-binding experiments on the eye sections, the slides were brought to 23°C and allowed to air-dry for 30 minutes. This procedure helped the adherence of the tissue sections to the slides.…”

“…After this time, the slides were removed from the carriers and taped in a suitable arrangement, together with [ 3 H]Microscale ® (Amersham, Arlington Heights, IL) radiation standards, into X-ray film cassettes in order to image the receptor autoradio-graphs. [18][19][20][21] The slides were then overlaid with a sheet of radiation-sensitive film (Hyperfilm ® [Amersham, Arlington Heights, IL]) in total darkness and the cassettes closed. Films were exposed to the film for 6 months at room temperature without intensifying screens in a leadshielded container in order to generate the receptor autoradiograms.…”

“…The competition data for various unlabeled prostaglandins obtained by image analysis for various human ocular tissues were analyzed using an iterative, nonlinear, curve-fitting program, as previously described and utilized. [18][19][20][21][22][23][24]34,36 The competition curves were plotted using the Origin ® computer program (Microcal, Northampton, MA) as previously described. [22][23]36 …”

“…[18][19][20][21] This technique requires small amounts of tissue and utilizes micrometer thick (10-20 m) sections (e.g., from human eyes) and receptor-or enzyme-specific radioligands to provide high-resolution information on receptor distribution in the various subregions of the tissue under study. Quantitative autoradiographic studies can also be employed to determine the pharmacological attributes of receptors, as previously demonstrated for the central nervous system, cardiovascular and renalvascular systems, [18][19][20][21] and recently for the FP prostaglandin 22,23 and ␤-receptors 24 in human eyes. This technique is particularly well suited for tissues that are difficult to dissect out and/or impractical to acquire in amounts necessary for in vitro homogenate-based binding experiments.…”

Aldosterone and high-NaCl diet modulate ClC-2 chloride channel gene expression in rat kidney

“…They were then divided in two groups of five rats. The animals in one group were maintained on the normal diet (control) and in the other group the rats were fed a highNa + diet containing 8.0 g/kg NaCl and drinking 9 g/l NaCl water for 5 days (high-Na + -5d) [1,24,27].…”