LIGHT MODULATES DOPAMINE-REGULATED WALSH INHIBITOR ACTIVITY AND DOPAMINE-DEPENDENT CYCLIC-AMP ACCUMULATION IN THE RABBIT RETINA

Abstract

The effect of various dopaminergic agents and related drugs on the actvity of the heat-stable inhibitor of cyclic AMP (cAMP)-dependent protein kinase (Walsh inhibitor) and on cAMP accumulation was studied in retinas of light- and dark-adapated rabbits. Both in the dark- and light-adapated rabbits low doses of apomorphine increased the retinal Walsh inhibitor activity; high doses of the drug decreased the Walsh inhibitory activity in dark-adapted rabbits, but were without effect in light-adapted animals. S-Sulpiride antagonized the effect of low doses of apomorphine on the Walsh inhibitor activity, and, in contrast to haloperidol (which was effective), did not affect the action of a high apomorphine dose. Selective agonists of dopamine (DA) D2-receptor, quinpirole and bromocriptine, increased the retinal Walsh inhibitor activity in both light- and dark-adapted animals, a selective D1-agonist, SKF 38393, decreased the inhibitor activity in dark- and did not significantly modify it in light-adapated animals. In in vitro experiments, carried out in the presence of theophylline, DA and apomorphine increased cAMP accumulation in pieces of the rabbit retina through activation of D1-receptors. The action of DA, apomorphine, and SKF 38398, was significanlty stronger in retinas of dark- than of light-adapated animals. Forskolin stimulated cAMP accumulation in a concentration-dependent manner, producing at 100 .mu.M increases of cAMP levels by approximately 5-fold. DA and SKF 38393 did not significantly modulate the action of 10 .mu.M forskolin, whereas apomorphine slightly decreased the forskolin effect. Of the two selective D2-receptor agonists, bromocriptine slightly decreased, and quinpirole had no effect on the forskolin action. The characteristics of the specific binding of [3H]spiroperidol were essentially the same in the retinas of dark- and light-adapted rabbits. Our data suggest that in light-adapted animals in the D1-receptors, or the effector mechanisms for regulation of the Walsh inhibitor activity, may be desensitized. Our results suggest also that in the rabbit retina there are probably no D2-receptors coupled negatively to adenylate cyclase, although a pharmacologically similar class of DA receptors seems to be involved in regulation of the Walsh inhibitory activity (in a way independent on environmental lighting).