Norepinephrine acts as D₁-dopaminergic agonist in the embryonic avian retina: Late expression of β₁-adrenergic receptor shifts norepinephrine specificity in the adult tissue

Dopamine is the main catecholamine found in the chick retina whereas norepinephrine is only found in trace amounts. We compared the effectiveness of dopamine and norepinephrine in promoting cyclic AMP accumulation in retinas at embryonic day 13 (E13) and from post-hatched chicken (P15). Dopamine (EC₅₀ = 10 μM) and norepinephrine (EC₅₀ = 30 μM), but not the β₁-adrenergic agonist isoproterenol, stimulated over seven-fold the production of cyclic AMP in E13 retina. The cyclic AMP accumulation induced by both catecholamines in embryonic tissue was entirely blocked by 2 μM SCH23390, a D₁ receptor antagonist, but not by alprenolol (β-adrenoceptor antagonist). In P15 retinas, 100 μM isoproterenol stimulated five-fold the accumulation of cAMP. This effect was blocked by propanolol (10 μM), but not by 2 μM SCH23390. Embryonic and adult retina display β₁ adrenergic receptor mRNA as detected by RT-PCR, but the β₁ adrenergic receptor protein was detected only in post-hatched tissue. We conclude that norepinephrine cross-reacts with D₁ dopaminergic receptor with affinity similar to that of dopamine in the embryonic retina. In the mature retina, however, D₁ receptors become restricted to activation by dopamine. Moreover, as opposed to the embryonic tissue, norepinephrine seems to stimulate cAMP accumulation via β₁-like adrenergic receptors in the mature tissue.