The cyclic AMP (cAMP)-dependent signaling accounts for the control of cellular cascades involved in many physiological functions, and a wealth of information is available on the cAMP system that operates in mammalian cells. Nevertheless, cAMP has a central role also in nonmammalian vertebrates and invertebrates. The present review aims at examining the information available on bivalve molluscs, from the first studies carried out in the early 1980s to the last progresses made in the present days. The major focus is on the structural and operational characteristics of the main actors of the signaling pathway, i.e., adenylyl cyclase, G proteins, and protein kinase A, and on the role played by the cyclic nucleotide on smooth muscle, heart, gills, gonads, and metabolism regulation. Moreover, recent evidence regarding the cAMP system as a target of environmental stress factors are discussed. It will become clear that cAMP does play a wide and important role in bivalve physiology. Several issues have been sufficiently clarified, although investigated only in a few model species. However, further fundamental aspects remain unknown, mainly regarding molecular features and interactions with other signaling pathways, thus requiring further elucidation. J. Exp. The discovery of cyclic AMP (cAMP) about 50 years ago was the crucial event leading to our current paradigm of second-messenger signaling, through which many hormones, neurotransmitters, odorants, and autocrine/paracrine regulators modulate physiological functions. Other second messengers were discovered from then on; however, cAMP has never left its center stage. Biological and genetic evidence point to roles for cAMP in a vast array of biological systems, including oogenesis and embryogenesis, development, hormone secretion, olfaction, cardiac contraction, smooth muscle relaxation, metabolism, etc. Therefore, understanding the cAMP-dependent pathway in all its parts became a scientific priority that prompted to a remarkable amount of studies and relevant achievements (Diel et al., 2008;Sadana and Dessauer, 2009). Admittedly, the pathway once considered simple and straightforward became very complex, thus requiring more and more sophisticated investigations mainly focused on mammalian cells. If this is easily understandable also for the implications of cAMP signaling in human health and possible therapeutic applications, the counterpart is a rather scarce knowledge of the system in nonmammalian vertebrates and invertebrates.The present review focuses on the cAMP-dependent pathway in bivalve molluscs, aimed at collecting and ordering the research outputs produced in this regard. Bivalve molluscs are the model animals currently studied in our laboratories, and we did experience such fragmented information. Moreover, growing interest is addressed to these animals as widely cultivated aquaculture species and sentinel organisms used for evaluating the environmental quality. Undoubtedly cAMP plays a role in these contexts and an organized set of information would be of be...
