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The solution for the so-called “calcium paradox” has been revealed 4 years ago, when we demonstrated the involvement of the interaction between Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling interaction) in this enigma. The “calcium paradox” emerged 4 decades ago, when numerous clinical studies have concluded that prescription of L-type Ca2+ Channel Blockers (CCBs) for hypertensive patients decreased arterial pressure, but produced stimulation of sympathetic hyperactivity. Indeed, initially these adverse effects of CCBs have been attributed to adjust reflex of arterial pressure, but this conclusion remained not completely satisfactory. The year of 2013 would change this history forever! Through an original experiment, we revealed that the “calcium paradox” phenomenon came from increased transmitter release from sympathetic neurons stimulated by CCBs due to its handling on the Ca2+/cAMP signalling interaction. It is now well-established that the signalling pathways mediated by Ca2+ and cAMP can interact, thus playing a vital role in cellular processes of mammalians. In the clinical pharmacology, it has opened novel opportunities for the development of pharmaceuticals more efficient, and safer, for treating neurodegenerative diseases. Then, the manipulation of Ca2+/cAMP signalling interaction could improve therapeutic strategies for stimulating synaptic transmission compromised by transmitter release deficit, and attenuating death of neurons. More recently, the manipulation of this interaction has been proposed by us to inhibit cancer progression, another interesting avenue for medical research.

international archives of clinical pharmacology

Novel Concepts for Clinical Pharmacology from "Calcium Paradox" due to Neuronal Interaction between Signalling Pathways Mediated by Ca2+ and cAMP from 1975 to 2017