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.