Noradrenaline, a transmitter candidate in the retina.

The occurrence, metabolism, uptake, and release of noradrenaline were studied in the bovine retina with the following results. (1) Small amounts of noradrenaline occur in the retina and are restricted to the area corresponding to the inner nuclear and plexiform layers. (2) Retinal tissue can metabolise [14C]dopamine to form quantities of [14C]noradrenaline. (3) [14C]Noradrenaline can also be partly metabolised to form [14C]normetanephrine. (4) When bovine retinas were incubated with 5 x 10(-7) M-[3H]noradrenaline for 20 min and processes for autoradiography, most of the label was associated with apparent nerve processes in the inner plexiform layer. Biochemical analysis showed that more than 95% of the label was noradrenaline. (5) [14C]Noradrenaline uptake saturated with increasing noradrenaline concentrations and followed Michaelis-Menten kinetics. This uptake could be accounted for by two processes, a high-affinity system with a Km1 of 5 x 10(-8) M and a Vmax1 of 0.193 pmol/mg/10 min and a low-affinity system with a Km2 of 6.3 x 10(-5) M and a Vmax2 of 0.109 nmol/mg/10 min. (6) Noradrenaline uptake was strongly dependent on temperature and sodium, less dependent on potassium, and independent of calcium and magnesium ions. (7) Centrally acting drugs, such as desipramine, imipramine, desmethylimipramine, and amitriptyline, inhibited noradrenaline uptake by more than 55% at the concentration of 5 x 10(-5) M. These drugs at the same concentration diminished dopamine uptake by less than 30%. (8) Noradrenaline uptake is stereospecific, the (-) isomer having a greater affinity for the uptake sites than the (+) isomer. (9) [14C]Noradrenaline in the retina could be released by increasing the external potassium concentration. This release was calcium-dependent and was blocked by 20 mM-cobalt chloride. The present studies could be interpreted as supporting the idea that noradrenaline acts as a transmitter in the retina.