Ca2+ and Camp: Do these Intracellular Messengers Work’Independently? Of Course Not, and the History Goes Ahead…

Abstract

Our group has been pioneering in exploring that the pharmacological handling of Ca2+/cAMP signalling interaction could be a better therapeutic method for increasing neurotransmission in psychiatric disorders, and stimulating neuroprotection for combating neurodegenerative diseases, such as Alzheimer´s disease. Indeed, Ca2+ is a classic intracellular second messenger, now well recognized as a ubiquitous molecule that controls several processes, including gene transcription, cell cycle regulation, mobility, apoptosis, neurotransmitter release and muscle contraction. In addition, cAMP, another vital intracellular messenger, modulates since cardiac contraction to neurotransmitter release. Do these intracellular messengers ´work´ independently? Of course not, and we demonstrated it! Through groundbreaking experiments (including one by accident!), our group discovered that the paradoxical effects (e.g. reduction of intracellular Ca2+ concentration, and enhancing of neurotransmitter release?!) produced by L-type Ca2+ channel blockers (CCBs) resulted from interferences on the Ca2+/ cAMP signalling interaction. Considering the widely use of CCBs as antihypertensive drugs, and for combating arrhythmia, the elucidation of these paradoxical effects proved to be very important (specially for clinical reasons). How does this history correlate to cancer field? Considering the notion that Ca2+/cAMP signalling interaction is a fundamental cellular process, which exists in many cell types, whether this interaction may be a novel therapeutic target to alter cancer tumor growth, angiogenesis and metastasis, without affecting normal cell physiology deserves special consideration. Thus, this editorial article highlights the latest advances made by our group in the field of Ca2+/cAMP signalling interaction.