L-745,870 suppresses the nighttime serotonin N-acetyltransferase activity in chick retina: in vivo evidence for agonist activity at D4-dopamine receptors

• Published in: Journal of neural transmission 2003-03, Vol.110 (3), p.219-227
• Main Authors: ZAWILSKA, J. B, ROSIAK, J, BEREZINSKA, M, NOWAK, J. Z
• Format: Article
• Language: English
• Subjects: Animals; Arylamine N-Acetyltransferase - antagonists & inhibitors; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Chickens; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Darkness; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Male; Pyridines - pharmacology; Pyrroles - pharmacology; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D4; Retina - drug effects; Retina - enzymology; Serotonin - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-002-0787-3

This study examined the in vivo activity of L-745,870 at dopamine (DA) D(4) receptors, using the chick retina as a model system. In dark-adapted retinas of various vertebrates, including hen, DA acting via D(4) receptors suppresses melatonin content and activity of serotonin N-acetyltransferase (AA-NAT, a key regulatory enzyme in melatonin synthesis). Systemic administration to chicks of quinpirole (0.1 mg/kg), a high affinity agonist of D(3)/D(4)-DA receptors, potently decreased the nighttime AA-NAT activity of the retina. The quinpirole-evoked decline in the enzyme activity was attenuated by L-745,870 (0.1-10 nmol/eye). In addition to this action, L-745,870 given to chicks either directly into the eye (0.03-10 nmol/eye) or intraperitoneally (0.5-5 mg/kg) decreased the nighttime AA-NAT activity of the retina in a dose-dependent manner. The suppressive effect of L-745,870 on retinal AA-NAT activity was blocked by 2-chloro-11-(4-methylpiperazino)dibenz[ b, f]oxepin, an antagonist of D(4)-DA receptors, but was not affected by raclopride, an antagonist of D(2)/D(3)-DA receptors. Altogether these results indicate that in chicks L-745,870, the potent putative D(4)-DA receptor antagonist, behaves in vivo as a partial D(4) agonist.