L-745,870 suppresses the nighttime serotonin N-acetyltransferase activity in chick retina: in vivo evidence for agonist activity at D4-dopamine receptors.
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.
Zawilska
J B
JB
Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland. jolantaz@amina1.zabpan.lodz.pl
Rosiak
J
J
Berezińska
M
M
Nowak
J Z
JZ
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003624:Darkness; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D012160:Retina / Q000187:drug effects* / Q000201:enzymology; D012701:Serotonin / Q000378:metabolism*
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D011725:Pyridines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012701:Serotonin; D001191:Arylamine N-Acetyltransferase