Our discovery of the involvement of the interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP interaction) in the neurotransmission and neuroprotection has produced new avenues in the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurological and psychiatric disorders, such as Alzheimer´s and Parkinson's diseases. Interestingly, this discovery initiated decades ago when numerous clinical studies have reported that use of L-type Ca2+ channel blockers (CCBs) by hypertensive patients decreased arterial pressure, but produced typical symptoms of sympathetic hyperactivity, such as tachycardia and increment of catecholamine plasma levels. Despite these adverse effects of CCBs have been initially attributed to adjust reflex of arterial pressure, during almost four decades this enigmatic phenomenon named calcium paradox remained unclear. In 2013, we discovered that this phenomenon was resulting of increment of transmitter release from sympathetic neurons and adrenal chromaffin cells, stimulated by CCBs due to its interference on the Ca2+/cAMP interaction. In this way, our discovery of the role of Ca2+/cAMP interaction in the neurotransmitter release, and neuronal death triggered by cytosolic Ca2+ overload, opened novel adventures for the development of new pharmacological strategies more effective for the treatment of neurological and psychiatric disorders resulting of neurotransmitter release deficit, and neuronal death.
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Bueno et al. (2017) studied this question.