Activation of D2 dopamine receptors in hen retina decreases forskolin-stimulated cyclic AMP accumulation and serotonin N-acetyltransferase (NAT) activity.
Dopamine (DA; 1-100 ?M) alone did not significantly stimulate cyclic AMP accumulation in the hen retina; however, in the presence of 0.3 ?M spiroperidol, it clearly increased it. DA, in a concentration-dependent manner, enhanced the stimulatory effect of forskolin (1 and 10 ?M), both in the absence and presence of a phosphodiesterase (PDE) inhibitor IBMX (0.5 mM). A selective D1-receptor blocker such as SCH 23390 antagonized the activating effect of DA when used at 1 ?M, and reversed the amine action from a stimulatory into an inhibitory effect when applied at 3 or 10 ?M concentration. Addition of 0.3 ?M spiroperidol further enhanced the DA action on cyclic AMP accumulation evoked by forskolin; however, spiroperidol used at 5 ?M concentration antagonized the potentiating effect of the amine. Selective agonists of DA D2-receptors such as quinpirole (LY 1715550; 0.01-10 ?M) and bromocriptine (1-100 ?M) decreased both basal levels and forskolin-stimulated cyclic AMP accumulation in a concentration-dependent manner in the absence and presence of 0.5 mM IBMX. Under daylight conditions, dibutyryl-cyclic AMP (1 mM) and a combination of 50?M forskolin and 0.1 mM IBMX (these drugs applied separately were only weakly active) significantly enhanced the activity of serotonin N-acetyltransferase (NAT) activity (the key regulatory enzyme in melatonin biosynthesis) in pieces of the hen retina. Quinpirole (0.001-10 ?M) inhibited the effect of forskolin (combined with IBMX) in a concentration-dependent and spiroperidol-sensitive manner, and did not modify the action of dibutyrylcyclic AMP. It is concluded that the hen retina possesses both types of DA receptors, i.e. D1 and D2, whose stimulation respectively increase and decrease cyclic AMP levels. These D2-receptors, which are negatively coupled to adenylate cyclase, seem to be involved in the regulation of NAT activity in the retina, and their activation leads to the inhibition of the enzyme induction.
Nowak
J Z
JZ
Department of Biogenic Amines, Polish Academy of Sciences, P-225, 90-950 Lodz, Poland.
Sek
B
B
Zurawska
E
E