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Pharmaceutical intervention on Ca2+/cAMP signaling interaction: benefits for combating neurodegeneration and diseases related to aging

Journal: International Journal of Human Anatomy (Vol.1, No. 1)

Publication Date:

Authors : ; ;

Page : 21-26

Keywords : Ca2+/cAMP signaling interaction; diseases related to aging;

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Abstract

The pharmaceutical intervention on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) could bring important benefits for combating neurodegeneration and diseases related to aging. This discovery emerged from classical neurotransmission studies using rodent vas deferens as a model. From classical reports using this model, the concept of Ca2+ -dependent processes involved in the neurotransmission (Ca2+ influx triggers muscle contraction and neurotransmitter release) is amply accepted. Thus, Ca2+ channel blockers (CCB) due to reduction of Ca2+ influx through L-type voltageactivated Ca2+ channels (VACC) should reduce neurotransmission. 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 by 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 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 neurodegenerative diseases, thus may stimulate the development of new pharmacological strategies to combat the diseases related to aging.

Last modified: 2018-05-15 15:41:44