A link among schizophrenia, diabetes, and asthma: Role of Ca2+/cAMP signaling

Abstract

Asthma has been associated with an increased risk for developing schizophrenia. In addition, schizophrenia has been associated with an increased risk for developing type 2 diabetes mellitus, resulting in an elevated cardiovascular risk and in a limited life expectancy. It is well discussed that dysregulations related to Ca²⁺ signaling could link these diseases, in addition to cAMP signaling pathways. Thus, revealing this interplay among schizophrenia, diabetes, and asthma may provide novel insights into the pathogenesis of these diseases. Publications involving Ca²⁺ and cAMP signaling pathways, schizophrenia, diabetes, and asthma (alone or combined) were collected by searching PubMed and EMBASE. Both Ca²⁺ and cAMP signaling pathways (Ca²⁺/cAMP signaling) control the release of neurotransmitters and hormones, in addition to airway smooth muscle contractility, then dysregulations of these cellular processes may be involved in these diseases. Taking into consideration, the experience of our group in this field, this narrative review debated the involvement of Ca²⁺/cAMP signaling in this link among schizophrenia, diabetes, and asthma, including its pharmacological implications.

Keywords: Asthma; Ca2+ channel blockers; Ca2+/cAMP signaling; diabetes; neurodegeneration; pharmacotherapy; schizophrenia.

Figure 1

Pharmacological modulation of Ca²⁺/cAMP signalling. Briefly, decreasing Ca²⁺ influx through L-type Ca²⁺ channels, e.g., endorsed by Ca²⁺ channel blockers, increases AC activity (and consequently elevating cAMP levels; named as Ca²⁺/cAMP signalling interaction), then these Ca²⁺ channel blockers-effects can be increased by cAMP-stimulating compounds (like PDEs inhibitors)

Figure 2

The Ca2+/cAMP signalling dysregulations and their consequences. Symbols - Up arrow: increasing; Down arrow: decreasing; (Ca2+)c: Intracellular concentration of Ca2+; (cAMP)c: Intracellular concentration of cAMP