UPTAKE AND ACCUMULATION OF 3H-NORADRENALINE IN ADRENERGIC NERVES OF RAT IRIS - EFFECT OF RESERPINE, MONOAMINE OXIDASE AND TYROSINE HYDROXYLASE INHIBITION

Isolated rat irides were incubated in Krebs-Ringer bicarbonate buffer containing 3H-noradrenaline (3H-NA) and the 3H-NA taken up was determined. The extracellular space determined with 14C-sorbitol was about 40% of the iris. The equilibration and clearing of the extracellular space occured within 15 min incubation time. Four pharmacologically different uptake models for NA were used: irides from untreated rats, nialamide pretreated rats, reserpine + nialamide pretreated rats and H44/68 (synthesis inhibitor) pretreated rats. Specific chemical determinations disclosed that very small amounts of metabolites are formed in the iris preparation after an in vitro incubation. It was concluded that there is an efficient uptake and accumulation of NA in adrenergic nerves of rat iris. The membrane pump seemed to be the dominant and most important mechanism for the initial uptake while the granular uptake mechanism was of importance for the total storage capacity and intraneuronal retention. Reserpine did not affect the axonal membrane uptake to any significant degree. After pretreatment with a synthesis inhibitor, H44/68, the uptake and accumulation of 3H-NA in the iris was only increased 10-20% compared to the untreated iris, indicating that the depleted NA stores were not completely refilled. The extraneuronal uptake was very small provided that the medium concentration of NA was not too high (10-6 M or lower). This uptake increased considerably in relation to the neuronal uptake when NA concentrations of 10-5 M of higher were used, although there was no true accumulation of amine in the tissue compared with the medium. © 1969.