In lower vertebrates, cone retinomotor movements occur in response to changes in lighting conditions and to an endogenous circadian clock. In the light, cone myoids contract, while in the dark, they elongate . In order to test the hypothesis that melatonin and dopamine may be involved in the regulation of cone movement, we have used an in vitro eyecup preparation from Xenopus laevis that sustains light-and dark-adaptive cone retinomotor movement . Melatonin mimics darkness by causing cone elongation . Dark-and melatonin-induced cone elongation are blocked by dopamine . Dopamine also stimulates cone contraction in dark-adapted eyecups. The effect of dopamine appears to be mediated specifically by a dopamine receptor, possibly of the D2 type . The dopamine agonist apomorphine and the putative D2 agonist LY171555 induced cone contraction . In contrast, the putative D, agonist SKF38393-A and specific a,-, a2-, and /3-adrenergic receptor agonists were without effect . Furthermore, the dopamine antagonist spiroperidol not only blocked light-induced cone contraction, but also stimulated cone elongation in the light. These results suggest that dopamine is part of the light signal for cone contraction, and that its suppression is part of the dark signal for cone elongation . Melatonin may affect cone movement indirectly through its influence on the dopaminergic system .

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A circadian clock modulates the functional organization of the Japanese quail retina. Under conditions of constant darkness, rods dominate electroretinogram (ERG) b-wave responses at night, and cones dominate them during the day, yielding a circadian rhythm in retinal sensitivity and rod-cone dominance. The activity of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, also exhibits a circadian rhythm in the retina with approximately threefold higher levels during the day than at night. The rhythm of tyrosine hydroxylase activity is opposite in phase to the circadian activity of tryptophan hydroxylase, the first enzyme in the melatonin biosynthetic pathway. We tested whether dopamine may be related to the physiological rhythms of the retina by examining the actions of pharmacological agents that effect dopamine receptors. We found that blocking dopamine D2 receptors in the retina during the day mimics the nighttime state by increasing the amplitude of the b-wave and shifting the retina to rod dominance. Conversely, activating D2 receptors at night mimics the daytime state by decreasing the amplitude of the b-wave and shifting the retina to cone dominance. A selective antagonist for D1 dopamine receptors has no effect on retinal sensitivity or rod-cone dominance. Reducing retinal dopamine partially abolishes rhythms in sensitivity and yields a rod-dominated retina regardless of the time of day. These results suggest that dopamine, under the control of a circadian oscillator, has a key role in modulating sensitivity and rod-cone dominance in the Japanese quail retina.

The effects of neuropeptide Y (NPY) on LHRH release from an immortalized cell line were investigated using a flow-through cell culture superfusion system. Immortalized hypothalamic GT1-7 cells were cultured for 72 h and superfused for a total of 180 min. In initial experiments, discrete 5-min pulses of NPY (10(-12)-10(-5) M) were administered to the cells. A clear dose-dependent stimulatory effect on NPY on LHRH release from the cells was observed with a calculated 50% effectiveness concentration of 33 nM. The stimulatory effects of brief NPY exposure were rapid and robust, e.g. reaching and maintaining levels of 173% over baseline for 20 min at the 10(-7) dose. The lowest dose of NPY that showed a significant effect was 10(-10) M; maximal responses were observed at 10(-6) M and reached a plateau thereafter. Control pulses of Dulbecco's modified Eagle's medium (DMEM) and 10(-6) M substance P or arg-vasopressin were also presented to the cells to serve as controls for our pulse protocol, and these challenges produced no significant LHRH responses. The NPY receptor antagonists, PYX1 and PYX2, at 10(-8) M, completely blocked the observed NPY responses in these cells. To assess the NPY receptor subtypes that mediate the NPY effects pharmacologically, GT1-7 cells were challenged with a Y1 receptor agonist, (Leu31Pro34)NPY, a Y2 receptor agonist, NPY(13-36), or peptide YY, at doses 10(-12)-10(-5) M. All four peptides stimulated LHRH release from GT1-7 cells with a rank-ordered potency of NPY = peptide YY > Y1 agonist = Y2 agonist. To examine possible signal transduction mechanism(s) involved in mediating this effect, pertussis toxin, RpcAMPs (cyclic adenosine-3'5'-monophosphothioate Rp diastereomer), Ca(2+)-free DMEM and TMB-8 (3, 4, 5-trimethoxybenzoic acid 8-(diethylamino) octylester) were used to treat the cells before and during superfusion with NPY. Treatment with pertussis toxin, RpcAMPs, and Ca(2+)-free DMEM did not significantly alter NPY-stimulated LHRH release responses to 10(-7) M NPY. However, the addition of 100 microM and 250 microM TMB-8 to Ca(2+)-free DMEM almost completely blocked this NPY effect, as did 10 microM ryanodine. Finally, the locus of action for this NPY effect was examined using tetrodotoxin to reduce action potential propagation in the GT1-7 cells. Tetrodotoxin treatment blocked the LHRH response to NPY by more than 50%.(ABSTRACT TRUNCATED AT 400 WORDS)