INTRANEURONAL AND EXTRANEURONAL ACCUMULATION OF SYMPATHOMIMETIC AMINES IN THE ISOLATED NICTITATING MEMBRANE OF THE CAT

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The accumulation of norepinephrine-H³ (NE-H³) in the isolated normal nictitating membrane of the cat was linearly related to bath concentrations which varied from 0.6 ng/ml to 100 µg/mi of dl-NE-H³. Experiments with denervated membranes showed that with low bath concentrations accumulation in the normal membrane was mainly due to intraneuronal accumulation, while extraneuronal accumulation occurred in both normal and denervated membranes when the bath concentration was increased to 1 µg/ml or more of dl-NE-H³. If it is assumed that extraneuronal accumulation is identical in normal and in denervated membranes, intraneuronal accumulation can be calculated as the difference in NE-H³ content between the normal and the denervated membrane. Intraneuronal accumulation was saturable at bath concentrations of about 1 µg/ml of dl-NE-H³. The sharp increase in the extraneuronal accumulation observed with higher concentrations of dl-NE-H³ in denervated membranes coincided with a pronounced relative decrease in the tissue content of 0-methylated metabolites-H³. Intraneuronally retained NE-H³ had a long half-life on wash out, while that of extraneuronally retained NE-H³ was only about 10 minutes. At least some of the norepinephrine which leaves the extraneuronal stores seems to be able to reach the receptors. The two types of accumulation were characterized pharmacologically. Intraneuronal accumulation was reduced by cocaine, phenoxybenzamine or pretreatment with reserpine and not affected by metanephrine, or block of catechol-O-methyltransferase or monoamine oxidase. Extraneuronal accumulation was reduced by metanephrine or phenoxybenzamine, increased after block of catechol-O-methyltransferase or monoamine oxidase and was unaffected by cocaine or pretreatment with reaerpine. Relative rates of extraneuronal accumulation were: isoproterenol-H³ > epinephrine-H³ = NE-H³.

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