Abstract
Isolated irides from nonalbino guinea pigs, when incubated with various concentrations of (-)-14C-ephedrine, accumulated 8 to 9 times more drug than irides from albino guinea pigs. Slightly pigmented irides accumulated intermediate amounts. Iris homogenate containing melanin granules also accumulated (-)-14C-ephedrine. During repeated washing of the nonpigmented iris, the accumulated drug was rapidly lost (T½ of 12 minutes), while that bound by pigmented iris was difficult to wash off. The sorbitol space was identical in the two types of irides. The accumulation of the drug by the pigmented iris appears to be a saturable process insensitive to cocaine but sensitive to temperature. The accumulation of (+)-14C-ephedrine was as great as that of the (-)-isomer. Vas deferens, a tissue which lacks melanin, either obtained from albino or nonalbino animals, accumulates equal amounts of (-)-14C-ephedrine. Chloroquine, a substance known to have high affinity for binding to pigmented tissues, reduced the accumulation of (-)-14C-ephedrine by the pigmented iris. Synthetic L-dopa-melanin also accumulated (-)-14C-ephedrine and its accumulation was reduced by chloroquine. Endogenous norepinephrine determined by chemical methods was the same in the two types of iris. In the iproniazid-treated tissue, the accumulation of (-)-14C-norepinephrine at low concentration was not significantly different in the two types of irides. Thus, the density of the adrenergic innervation may be similar in pigmented and nonpigmented irides. No metabolic products of (-)-14C-ephedrine were detected in the extract from the two types of irides. It is suggested that in the pigmented iris melanin appears to be a site of loss for the (-)-ephedrine, hence a lesser concentration of the drug will be available for interaction with the adrenergic neurons or the pharmacologic receptors and lesser mydriatic effects will be produced. In the nonpigmented (albino) iris, lacking melanin, relatively higher concentration of ephedrine will be available for interaction with neurons or receptors to produce a relatively greater mydriatic effect.
Footnotes
- Received April 13, 1972.
- Accepted October 5, 1973.
- © 1974 by The Williams & Wilkins Co.
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