Melatonin inhibitory effect on cAMP accumulation in the chick retina development

Abstract

The influence of melatonin on the developmental pattern of functional nicotinic acetylcholine receptors was investigated in embry-onic 8-day-old chick retinal cells in culture. The functional response to acetylcholine was measured in cultured retina cells by microphysiometry. The maximal functional response to acetylcho-line increased 2.7 times between the 4th and 5th day in vitro (DIV4, DIV5), while the Bmax value for [ 125 I]-α-bungarotoxin was reduced. Despite the presence of α8-like immunoreactivity at DIV4, functional responses mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors were observed only at DIV5. Mecamyla-mine (100 µM) was essentially without effect at DIV4 and DIV5, while dihydro-ß-erythroidine (10-100 µM) blocked the response to acetylcholine (3.0 nM-2.0 µM) only at DIV4, with no effect at DIV5. Inhibition of melatonin receptors with the antagonist luzindole, or melatonin synthesis by stimulation of D4 dopamine receptors blocked the appearance of the α-bungarotoxin-sensitive response at DIV5. Therefore, α-bungarotoxin-sensitive receptors were expressed in retinal cells as early as at DIV4, but they reacted to acetylcholine only after DIV5. The development of an α-bungaro-toxin-sensitive response is dependent on the production of mela-tonin by the retinal culture. Melatonin, which is produced in a tonic manner by this culture, and is a key hormone in the temporal organization of vertebrates, also potentiates responses mediated by α-bungarotoxin-sensitive receptors in rat vas deferens and cerebellum. This common pattern of action on different cell models that express α-bungarotoxin-sensitive receptors probably reflects a more general mechanism of regulation of these receptors. Correspondence

MT3 melatonin binding site, MT1 and MT2 melatonin receptors are present in oocyte, but only MT1 is present in bovine blastocyst produced in vitro

“…This stimulates phosphoinositide turnover and, by others means, inhibits the guanylate cyclase enzyme. Therefore, MT1 and MT2 signaling pathways can induce PKC activation by Ca 2+ waves, in parallel with the inhibition of the cAMP pathways [41,42]. …”

“…MT1 and MT2 inhibit the adenylate cyclase enzyme activity and are able to activate PKC, which consequently has proven to improve nuclear maturation and the quality of IVP blastocysts. The pM concentration range of melatonin observed to affect the cleavage and blastocysts formation rates is suggestive of the melatonin action on the MT1 receptor [41]. Interestingly, the MT1 melatonin receptor was characterised by autoradiography and immunocytochemistry in early day seven blastocysts, demanding further investigations as to its constitutive activity at this embryonic age, which will largely enhance the understanding about melatonin influence on bovine embryonic development.…”

Ocular disorders and the utility of animal models in the discovery of melatoninergic drugs with therapeutic potential

“…Myopia Chicken [36] Diabetes Sprague-Dawley rat diabetic induced [21,22] Wistar rat diabetic induced [42] Radiation-induced OD Rabbit [23] Cataracts Sprague-Dawley rat cataracts induced by GSH inhibition [24] UV B irradiation [44] Gamma irradiation [46] Selenite injection [47] Glaucoma Chronic, moderately elevated IOP rat Hypertonic solution microinjection [75] Episcleral veins cauterization [76] Hyaluronic acid injections [79,80] Glaucomatous induced CS rat [83] New Zeeland normotensive rabbit [62,91,92] Laser-induced glaucomatous monkey [86] Chicken [89] Optic nerve transection mouse [82] Uveitis Cat Intravitreal Injections of Bacterial lipopolysaccharide [94,96] Hamster Pig Bovine serum albumin [95] Hypoxia-ischemia Rat and Pig retinal ischemia model [98][99][100] Retinitis pigmentosa (rds/rds) mouse [110] P23H rat [111] Dystrophic rat RCS [112] Retinal detachment Hyaluronic acid-induced retinal detachment mouse [113] Proliferative vitreoretinopathy Pre-injected platelet-rich plasma pigmented rabbit [116] OD: Ocular disorders.…”

“…Second messenger studies performed in chick retinas demonstrate that the stimulation of MT 3 by 5-MCA-NAT increases the activation of adenylate cyclase (AC) pathway [88], as opposed to the receptor MT 2 (Mel1b), classically negatively coupled to AC [89].…”

Serotonin receptors are selectively expressed in the avian germ cells and early embryos

“…In contrast with serotonin, the activation of melatonin receptors usually results in the downregulation of cAMP (Slanar et al, 2000;Sampaio, 2008;Dauchy et al, 2009;Hardeland, 2009). Both cAMP and Ca 2+ play a regulatory role in oocyte activation and maturation, so both molecules influence the process of oocyte development.…”