Barbara R. Grubb

Electrical PD, short-circuit current and fluxes of Na and Cl across avian intestine.

Summary1.In vitro measurements were made of transmural potential difference (PD), short-circuit current (Isc), resistance and unidirectional fluxes of22Na and36Cl across the duodenum, jejunum, ileum and colon of normal sodium-replete domestic fowl (Gallus domesticus).2.The PD ranged from about 1 mV across the duodenum to 8mV across the colon while theIsc was, respectively, 2.8 and 64 μA · cm−2. The jejunum and ileum exhibited values between these extremes.3.Unidirectional fluxes (under short-circuit conditions) of Na and Cl were lowest across the duodenum where there was no evidence of active transport of these ions. Unidirectional fluxes of Na and Cl were less across the jejunum than across the ileum or colon. A net active transport of Na (but not Cl) was observed in the ileum (=106% of theIsc) and colon (=50% ofIsc).4.The possible physiological significance of these observations in the domestic fowl are discussed and are compared to that of a mammal, the rabbit.

Accumulation of cadmium by the eye with special reference to the lens

Subcutaneously administered Cd2+ (in vivo) was accumulated in the eyes of rabbits. The concentration was greatest in the iris-ciliary body, followed by the retina, cornea, and lens. It was also present in the vitreous humor, but was not detectable in the aqueous humor. Cd2+ in the bathing medium in vitro was toxic to the lens (tissues gained Na and lost K) at 10(-3) M, for 24 hr incubation, or 10(-5) M, for 7 days. Cadmium-109 was gradually accumulated by the lens in vitro (the process may be saturable), but with 10(-7) M Cd in the medium (similar to the vitreous in Cd-treated rabbits) 100 times less was taken up in 24 hr than in the 28-day in vivo experiments. Cadmium-109 in vitro was almost confined to the outer 30 to 50% of the lens tissue. Cadmium-109 was able to reenter the bathing medium, and its efflux was not changed by the presence of external Cd, suggesting that substantial specific binding was not occurring. Efflux could be reduced by lanthanum so that it may follow pathways similar to those used by Ca and Zn.

Tissue distribution of subcutaneously administered aluminum chloride in weanling rabbits

The purpose of our investigation was to determine blood and tissue levels of aluminum (Al) in normal young rabbits. Furthermore, we wished to determine tissue distribution and accumulation of Al as related to its blood concentration in Al-dosed rabbits. The levels of Al accumulated were determined in different tissues of growing rabbits after continuous subcutaneous administration of Al chloride (3.78 mg/d) for 28 d. No signs of toxicity were apparent from comparisons of hematocrit or weight gain between control and Al-dosed rabbits. The largest concentration of the Al was observed in bone, which was also found to have the highest levels in the control rabbit tissues. Following bone, the experimental animals showed the greatest increase of Al levels in kidney cortex, kidney medulla, liver, testes, skeletal muscle, heart, brain white matter, and brain hippocampus, in that order. No significant difference was found in brain grey matter between control and experimental animals. As the brain tissue of the Al-treated animals had the lowest Al level of the tissues measured, it appears that there is a partial blood-brain barrier to entry of Al.

Exchanges of lead in vitro by the rabbit crystalline lens.

Lead (using 203Pb as a tracer) is accumulated by rabbit lenses in vitro. This accumulation was time and concentration-dependent and could be inhibited by La3+. The results suggest that the process involves diffusion, but an interaction with anionic sites on the cell membranes may be involved. Tissue saturation concentrations of Pb were six times greater at 10(-5) M Pb as compared with 10(-6) M suggesting that the affinity of the metal ion for tissue ligands is quite low, but comparable to that in other tissues. Loss of accumulated 203Pb was slightly increased by La3+ suggesting that some binding to the plasma membrane is occurring. The thiol agent dithiothreitol considerably enhanced loss of 203Pb. Exposure of lenses to 10(-4) M Pb for 2 days resulted in an increased accumulation of sodium and loss of potassium, but lenses remained viable in 10(-5) M Pb for at least 3 days.

Tissue accumulation of cadmium as a function of blood concentration

We have provided data relating Cd concentration in tissue to about a 40-fold range in blood Cd concentration. Osmotic pumps containing cadmium chloride were subcutaneously implanted in male New Zealand white rabbits. The pumps continuously delivered either 0.15 or 1.5 mg Cd/d. Blood and plasma levels of Cd were measured weekly throughout the study. After 28 d, the rabbits were killed and tissue concentrations of Cd determined by atomic absorption spectrophotometry. Less than 10% of the total Cd in the blood was carried in the plasma, the remainder was associated with the blood cells, where it was bound mainly to metallothionein. We found the blood and tissue levels of Cd were correlated for each tissue we investigated. There was a wide range in affinity of the tissues for Cd; liver and kidney had the highest Cd uptake, whereas brain affinity was about 500 times less than liver.

Avian colonic ion transport: effects of corticosterone and dexamethasone.

Summary1.Corticosterone, a natural corticosteroid hormone in birds, when injected into domestic fowl (Gallus domesticus) (2000 μg·kg−1, 4–5 h before experiment) increases both the basal Isc (short-circuit current) and amiloride-sensitive Isc as well as the PD across the colon in vitro. Dexamethasone, a synthetic analogue (650 μg·kg−1, 4–5 h before experiment) also increases the basal and amiloride-sensitive Isc as well as PD in these preparations.2.In marked contrast, longer term injection or infusion of dexamethasone (650 μg·kg−1) for 3 or more days caused a decline in basal Isc and PD (the PD often reversed with the serosal side becoming electronegative) and a drop in resistance. However in these preparations, the amiloride-sensitive Isc was significantly elevated which could be accounted for by an increase in net Na flux.3.No significant change occurs in net flux of Cl or K although unidirectional fluxes in both directions were increased for both ions in birds given dexamethasone for 3 days.4.A disparity between the basal Isc and the amiloride-sensitive Isc appeared in these preparations from dexamethasone injected birds reflecting the transport of other ions, possibly HCO3− or H+. The possible role of corticosterone in mineral metabolism of birds is discussed.

Experimental hypercupremia does not result in increases in copper in lens, iris, or ocular fluids

Rabbits were continuously administered copper sulfate via subcutaneously implanted osmotic pumps. After one month, plasma, liver, ocular tissues and fluids were analyzed for copper by atomic absorption spectrophotometry. No elevation in copper content of the ocular fluids, lens or iris was noted although, dose-related increases were seen in the plasma and liver indicating that the copper was absorbed and disseminated systemically. It is likely that excess copper, like that which is normally ingested and absorbed, is largely protein-bound in the circulation, preventing crossing of the blood-ocular barrier.

Ocular chrysiasis: accumulation of gold in the rabbit eye

Gold entered the eye and was accumulated in the aqueous humor, iris-ciliary body, and cornea (measured by flameless atomic absorption spectroscopy) of rabbits given gold sodium thiomalate by subcutaneous infusion for 4 weeks. It was not detected following such exposure in the vitreous humor, lens or retina. The concentration of gold in the cornea was quite high, about 25% of that in the liver. The concentration in the aqueous humor was only about 2.5% of that in the plasma, which is similar to the fraction of gold (5%) that is not bound to plasma proteins.

Lead in detectable amounts was not observed in ocular fluids or the crystalline lens

An earlier report described the presence of high concentrations of lead in the bovine eye. However, we have been unable to detect this heavy metal in the ocular fluids or lenses of rabbits dosed with Pb, despite the appearance of high concentrations in blood, liver, and brain. We were also unable to detect it in lenses from cattle, horses, dogs, or four elderly humans. The possibility of environmental lead exerting toxic effects in the eye thus appears to be minimal.

Relationship of transmural electrical parameters to the luminal Na concentration in the colon of the fowl (Gallus domesticus).

SummaryElectrical parameters: PD, resistance,Isc and amiloride-sensitive-Isc across the fowl colon (in vitro) change in response to the Na content of the diet. On a low-Na diet these changes appear to reflect increases in ion transport, especially amiloride-inhibitable Na transport. In vitro the magnitudes of the changes are related to the Na concentration in the luminal (mucosal) fluid and in birds on a low-Na diet peak at a concentration of about 12.5 mM. Such Na concentrations are similar to those in the colonic fluid of Na-deprived birds. Typical Michaelis-Menten kinetics do not appear to apply, possibly reflecting a local adaptation of the ion transport process in response to its external Na concentration.