Light Stimulates Tyrosine Hydroxylase Activity and Dopamine Synthesis in Retinal Amacrine Neurons

Pm, Iuvone; Galli, CL; Garrison-Gund, C. K.; Neff, Norton H.

doi:10.1126/science.30997

Cited by 383 publications

(181 citation statements)

References 7 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…These observations confirm that the majority of the DA in the bowel is not of sympathetic origin because the concentration of DA does not decrease when the sympathetic nerves degenerate. The increased tissue content of DOPAC in the extrinsically denervated bowel is consistent with the idea that the turnover of DA increases after denervation, possibly because dopaminergic neurons become more active; however, as usually occurs when catecholaminergic neurons are stimulated, an increase in transmitter biosynthesis compensates for the stimulation-induced transmitter release to maintain near constancy in the stores of the transmitter (Weiner, 1970;Molinoff and Axelrod, 1971;Iuvone et al, 1978).…”

Section: Effects Of Extrinsic Denervation On Enteric Da and Dopacsupporting

confidence: 66%

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Li¹,

Pham²,

Tamir³

et al. 2004

J. Neurosci.

175

173

View full text Add to dashboard Cite

The existence of enteric dopaminergic neurons has been suspected; however, the innervation of the gut by sympathetic nerves, in which dopamine (DA) is the norepinephrine precursor, complicates analyses of enteric DA. We now report that transcripts encoding tyrosine hydroxylase (TH) and the DA transporter (DAT) are present in the murine bowel (small intestine Ͼ stomach or colon; proximal colon Ͼ distal colon). Because sympathetic neurons are extrinsic, transcripts encoding TH and DAT in the bowel are probably derived from intrinsic neurons. TH protein was demonstrated immunocytochemically in neuronal perikarya (submucosal Ͼ Ͼ myenteric plexus; small intestine Ͼ stomach or colon). TH, DA, and DAT immunoreactivities were coincident in subsets of neurons (submucosal Ͼ myenteric) in guinea pig and mouse intestines in situ and in cultured guinea pig enteric ganglia. Surgical ablation of sympathetic nerves by extrinsic denervation of loops of the bowel did not affect DAT immunoreactivity but actually increased numbers of TH-immunoreactive neurons, expression of mRNA encoding TH and DAT, and enteric DOPAC (the specific dopamine metabolite). The fetal gut contains transiently catecholaminergic (TC) cells. TC cells are the proliferating crest-derived precursors of mature neurons that are not catecholaminergic and, thus, disappear after embryonic day (E) 14 (mouse) or E15 (rat). TC cells appear early in ontogeny, and their development/survival is dependent on mash-1 gene expression. In contrast, the intrinsic TH-expressing neurons of the murine bowel appear late (perinatally) and are mash-1 independent. We conclude that the enteric nervous system contains intrinsic dopaminergic neurons that arise from a mash-1-independent lineage of noncatecholaminergic precursors.

show abstract

Section: Effects Of Extrinsic Denervation On Enteric Da and Dopacsupporting

confidence: 66%

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Li¹,

Pham²,

Tamir³

et al. 2004

J. Neurosci.

175

173

View full text Add to dashboard Cite

show abstract

“…Note that this change in coupling in response to light-adaptation would be opposite to that which is observed in the AII amacrine cell . Dopamine signaling is known to increase in lightadapted retina (Kramer, 1971;Iuvone et al, 1978;Dearry & Burnside, 1986) and to cause uncoupling in the AII amacrine cell via D1-type receptors (Hampson et al, 1992). If dopamine also influences the phosphorylation of the Cx35 giant gap junctions we predict that it would do so via D2/D4-type dopamine receptors, such as those found in photoreceptors (Cohen et al, 1992) and dopaminergic interplexiform cells (Harsanyi & Mangel, 1992) and which cause a decrease in cAMP signaling through a g i protein.…”

Section: Discussionmentioning

confidence: 98%

Connexin 35/36 is phosphorylated at regulatory sites in the retina

Kothmann

Li²,

Burr

et al. 2007

Vis Neurosci

View full text Add to dashboard Cite

Connexin 35/36 is the most widespread neuronal gap junction protein in the retina and central nervous system. Electrical and/or tracer coupling in a number of neuronal circuits that express this connexin are regulated by light adaptation. In many cases the regulation of coupling depends on signaling pathways that activate protein kinases such as PKA, and Cx35 has been shown to be regulated by PKA phosphorylation in cell culture systems. To examine whether phosphorylation might regulate Cx35/36 in the retina we developed phospho-specific polyclonal antibodies against the two regulatory phosphorylation sites of Cx35 and examined the phosphorylation state of this connexin in the retina. Western blot analysis with hybrid bass retinal membrane preparations showed Cx35 to be phosphorylated at both the Ser110 and Ser276 sites, and this labeling was eliminated by alkaline phosphatase digestion. The homologous sites of mouse and rabbit Cx36 were also phosphorylated in retinal membrane preparations. Quantitative confocal immunofluorescence analysis showed gap junctions identified with a monoclonal anti-Cx35 antibody to have variable levels of phosphorylation at both the Ser110 and Ser276 sites. Unusual gap junctions that could be identified by their large size (up to 32 μm 2 ) and location in the IPL showed a prominent shift in phosphorylation state from heavily phosphorylated in nighttime, dark-adapted retina to weakly phosphorylated in daytime, light-adapted retina. Both Ser110 and Ser276 sites showed significant changes in this manner. Under both lighting conditions other gap junctions varied from non-phosphorylated to heavily phosphorylated. We predict that changes in the phosphorylation states of these sites correlate with changes in the degree of coupling through Cx35/36 gap junctions. This leads to the conclusion that connexin phosphorylation mediates changes in coupling in some retinal networks. However, these changes are not global and likely occur in a cell type-specific or possibly a gap junction-specific manner.

show abstract

“…Dopamine decreases the response of horizontal cells to full-field stimulation (Mange1 and Dowling, 1987) and increases the transepithelial potential of RPE cells and the c-wave amplitude (Gallemore and Steinberg, 1990;Rudolf et al, 1992). Melatonin is synthesized and released in retina in darkness, and in some species, under the influence of a circadian clock (Hamm and Menaker, 1980;Besharse and Iuvone, 1983;Redburn and Mitchell, 1989), while dopamine synthesis and release in retina is stimulated by steady or flickering light (Kramer, 1971;Iuvone et al, 1978;Dowling and Watling, 1981;Parkinson and Rando, 1983;Godley and Wurtman, 1988;Boatright et al, 1989). Melatonin inhibits dopamine synthesis and release (Dubocovich, 1983;Nowak, 1988;Nowak et al, 1992;Boatright et al, 1994), and melatonin synthesis and release are inhibited by dopamine (Iuvone and Besharse, 1986;Iuvone et al, 1987Iuvone et al, , 1990Zawilska and Iuvone, 1989;Cahill and Besharse, 1991).…”

mentioning

confidence: 99%

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Iuvone

Gan

1995

J. Neurosci.

View full text Add to dashboard Cite

The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2- iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine- stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation. These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.

show abstract

Light Stimulates Tyrosine Hydroxylase Activity and Dopamine Synthesis in Retinal Amacrine Neurons

Cited by 383 publications

References 7 publications

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Connexin 35/36 is phosphorylated at regulatory sites in the retina

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Contact Info

Product

Resources

About