Dopamine D4 receptors regulate intracellular calcium concentration in cultured chicken cone photoreceptor cells: Relationship to dopamine receptor-mediated inhibition of cAMP formation

Abstract

Dopamine is a retinal neuromodulator secreted from amacrine and interplexiform cells. Activation of dopamine D4 receptors on photoreceptor cells reduces a light-sensitive pool of cAMP. The aim of present study was to evaluate the role of dopamine receptors and cAMP in the regulation of intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in photoreceptor cells of chick retina. Retinal cells from 6 day-old chicken embryos were isolated and cultured for 5-7 days prior to experiments. Cone photoreceptors were the predominant cell type in these cultures. Dopamine and agonists of dopamine D4 receptors suppressed K + -stimulated uptake of 45 Ca 2+ and [Ca 2+ ] i , measured with the Ca 2+ -sensitive fluorescent dye fura-2 AM. The effects of the agonists were blocked by dopamine D2/D4 receptor antagonists or by pertussis toxin. 8Br-cAMP, a cell permeable analog of cAMP, had no effect on inhibition of K + -stimulated 45 Ca 2+ influx or [Ca 2+ ] i by dopamine D2/D4 receptor agonists. Quinpirole inhibited the increase in cAMP level elicited by K + , which requires Ca 2+ influx through voltage-gated Ca 2+ channels, but not that induced by the calcium ionophore A23187. Moreover, dopamine had no effect on either forskolin-stimulated or Ca 2+ /calmodulin-stimulated adenylyl cyclase activity in cell membranes prepared from the cultured cells. These data indicate that the decrease of cAMP elicited by dopamine D4 receptor stimulation may be secondary to decreased [Ca 2+ ] i .

Melatonin: An underappreciated player in retinal physiology and pathophysiology

“…This effect of light appears to be partially a direct effect on photoreceptor cells, combined with an effect of dopamine. Dopamine is released from amacrine and interplexi form cells in response to light and acts on dopamine D4 receptors on the photoreceptor cells to further suppress cyclic AMP synthesis and Ca 2+ levels and to inhibit melatonin biosynthesis (Cohen et al, 1992; Zawilska et al, 1994; Tosini and Dirden, 2000; Nir et al, 2002; Ivanova et al, 2008). Such tight control of retinal melatonin levels suggests that high melatonin levels during the light-phase may be deleterious for the photoreceptor cells (Wiechmann and O’Steen, 1992; Sugarawa et al, 1998).…”

Melatonin and amfenac modulate calcium entry, apoptosis, and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation (405 nm)

“…12 The protective effect of melatonin is mediated by its interaction with a family of G-protein coupled receptors. 13 Increasing evidence demonstrates melatonin deficiency has a key role in the pathogenesis of AMD and in the present useful approach for melatonin in preventing this disease. However, the mechanisms by which melatonin may affect the pathophysiology of the retina is not wellunderstood today.…”

Thyroid hormone and adrenergic signaling interact to control pineal expression of the dopamine receptor D4 gene (Drd4)

“…Members of the D2-like receptor family, the Drd2, Drd3 and Drd4 receptors, are known to inhibit adenylate cyclase activity via a G i mechanism (Missale et al, 1998) and also to act independently of cAMP (Scarselli et al, 2001, Gu et al, 2006, Mei et al, 1995, Tang et al, 1994). In the retina, Drd4 appears to modulate phototransduction through a mechanism that requires cAMP (Klitten et al, 2008, Ivanova et al, 2008, Nir et al, 2002, Nir et al, 2001). …”