Bivalve metamorphosis is a developmental transition from a free-living larva to a benthic juvenile (spat), regulated by a complex interaction of neurotransmitters and neurohormones such as L-DOPA and epinephrine (catecholamine). We recently suggested an N-Methyl-D-aspartate (NMDA) receptor pathway as an additional and previously unknown regulator of bivalve metamorphosis. To explore this theory further, we successfully induced metamorphosis in the Pacific oyster, Crassostrea gigas, by exposing competent larvae to L-DOPA, epinephrine, MK-801 and ifenprodil. Subsequently, we cloned three NMDA receptor subunits CgNR1, CgNR2A and CgNR2B, with sequence analysis suggesting successful assembly of functional NMDA receptor complexes and binding to natural occurring agonists and the channel blocker MK-801. NMDA receptor subunits are expressed in competent larvae, during metamorphosis and in spat, but this expression is neither self-regulated nor regulated by catecholamines. In-situ hybridisation of CgNR1 in competent larvae identified NMDA receptor presence in the apical organ/cerebral ganglia area with a potential sensory function, and in the nervous network of the foot indicating an additional putative muscle regulatory function. Furthermore, phylogenetic analyses identified molluscan-specific gene expansions of key enzymes involved in catecholamine biosynthesis. However, exposure to MK-801 did not alter the expression of selected key enzymes, suggesting that NMDA receptors do not regulate the biosynthesis of catecholamines via gene expression.

双壳类动物的变态是从自由活动的幼虫到底栖幼体（裂口）的发育过渡，受神经递质和神经激素（例如L-DOPA和肾上腺素（儿茶酚胺））的复杂相互作用所调节。我们最近提出了N-甲基-D-天冬氨酸（NMDA）受体途径，作为双壳类变态的附加且以前未知的调节剂。为了进一步探索该理论，我们通过将有能力的幼虫暴露于L-DOPA，肾上腺素，MK-801和艾芬地尔，成功地诱导了太平洋牡蛎Crassostrea gigas的变态。随后，我们克隆了三个NMDA受体亚基CgNR1，CgNR2A和CgNR2B，序列分析表明功能性NMDA受体复合物的成功组装并与天然激动剂和通道阻滞剂MK-801结合。NMDA受体亚基在变形幼虫和幼鱼中在有感受力的幼虫中表达，但该表达既不自我调节也不被儿茶酚胺调节。CgNR1的原位杂交在有能力的幼虫中，NMDA受体在顶端器官/脑神经节区域存在NMDA受体，并具有潜在的感觉功能，而在脚的神经网络中则表明附加的假定的肌肉调节功能。此外，系统发育分析确定了儿茶酚胺生物合成中涉及的关键酶的软体动物特异性基因扩展。但是，暴露于MK-801不会改变所选关键酶的表达，这表明NMDA受体不通过基因表达来调节儿茶酚胺的生物合成。