新生儿及儿科医学

抽象的

Novel Concepts for Neurology and Medicine from the Interaction between Signalling Pathways Mediated by Ca2+ and cAMP: An Intriguing History

Leandro BB and Afonso C

It is now well-established that the signalling pathways mediated by Ca2+ and cAMP can interact (Ca2+/cAMP signalling interaction), thus playing a vital role in cellular processes of mammalians. In the neurology and medicine, it has opened novel opportunities for the development of pharmaceuticals more efficient, and safer, for treating neurodegenerative diseases. The solution for the so-called “calcium paradox” has been revealed 4 years ago, when we demonstrated the involvement of the 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. 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.