Afonso Caricati-Neto and Leandro Bueno Bergantin
Clinical research plays an important role in medical sciences by determining the safety and efficiency of medications, devices and diagnostic products for human use. Our discovery of the interactions between intracellular signaling pathways as mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) in neurotransmission could help improve clinical research. This discovery emerged from classical neurotransmission studies using rodent vas deferens as a model. In addition, the concept of Ca2+-dependent muscle contraction (Ca2+ influx triggers muscle contraction) is amply accepted. Thus, Ca2+ channel blockers (CCB) should reduce muscle contraction. Nonetheless, using this model, some studies performed since 1975 reported that reduction of Ca2+ influx by low concentrations of CCB (verapamil, diltiazem or nifedipine) produced a paradoxical increase of the contractions mediated sympathetic nerves, a phenomenon known as “calcium paradox”. Recent studies using adrenal chromaffin cells have also demonstrated that CCB caused a paradoxical increase of the catecholamine release. Because these compounds are blocking the L-type voltage-activated Ca2+ channels (VACC), an augmented nerve-mediated response due to increased neurotransmitter release was an unexpected outcome. In 2013, we revealed that the Ca2+/cAMP signaling interaction could properly explain the so-called “calcium paradox”. The original paper published by us in Cell Calcium (2013) has appeared four times in ScienceDirect TOP 25 Hottest Articles lists. In conclusion, these findings may significantly impact on cardiovascular and neurodegenerative diseases, cancer, stem cell-based therapies and many other diseases, and may stimulate the development of new pharmacological strategies to combat these diseases.
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