Melatonin synthesis in chicken retina: effect of kainic acid-induced lesions on the diurnal rhythm and D2-dopamine receptor-mediated regulation of serotonin N-acetyltransferase activity.
The effect of kainic acid (KA)-induced lesions of retinal neurons on regulation of serotonin N-acetyltransferase (NAT) activity in chicken retina was investigated. Although NAT activity was higher in KA-lesioned retinas than in controls, the pattern of diurnal variation of enzyme activity throughout 36 h of constant darkness was similar for both tissues. Quinpirole, a selective D2-dopamine receptor agonist, inhibited the nocturnal increase of NAT activity in both control and KA-treated retinas. Quinpirole was significantly more potent in KA-treated retinas than in controls; the ED50 value for quinpirole was 3 times lower in KA-treated retinas than in control tissues. KA treatment markedly reduced retinal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). We conclude that: (1) NAT activity in retina is localized primarily to KA-insensitive cells, presumably photoreceptors; (2) KA-sensitive inner retinal neurons are not essential to the maintenance of the circadian rhythm of NAT activity; and (3) KA-induced lesions of retinal cells result in supersensitivity of D2-dopamine receptors regulating NAT activity in a mechanism that involves adaptive changes following a decline in retinal dopamine neurotransmission.
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
J B
JB
Zawilska
P M
PM
Iuvone
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects*; D003624:Darkness; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology*; D008027:Light; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D012016:Reference Values; D012160:Retina / Q000187:drug effects / Q000201:enzymology*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D007608:Kainic Acid