Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca²⁺ mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.

Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca²⁺ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca²⁺, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca²⁺-ATPase (PMCA), sarco/endoplasmic Ca²⁺-ATPase (SERCA) and secretory pathway Ca²⁺-ATPase (SPCA) are considered efficient line of defense against abnormal Ca²⁺ rises. However, their role is not limited only to Ca²⁺ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca²⁺-ATPases to neuropathology, with a special emphasis on mental diseases.