Since V2 receptor Gs type, why does lithium which acts on Gq affect it?

Lithium is a medication commonly used to treat bipolar disorder and other psychiatric conditions. It is known to exert its therapeutic effects through various mechanisms, including inhibition of the enzyme inositol monophosphatase (IMPase), which leads to decreased levels of inositol triphosphate (IP3) and diacylglycerol (DAG). These second messengers are involved in the activation of the Gq protein-coupled receptors (GPCRs), which can lead to increased intracellular calcium levels and activation of downstream signaling pathways.

The V2 receptor, on the other hand, is a Gs protein-coupled receptor that mediates the effects of the antidiuretic hormone (ADH) on the kidney. Activation of the V2 receptor by ADH leads to the activation of the Gs protein, which stimulates adenylate cyclase and increases intracellular levels of cyclic AMP (cAMP). This, in turn, leads to the activation of protein kinase A (PKA) and other downstream signaling pathways that promote water reabsorption in the kidney.

While the V2 receptor is primarily a Gs protein-coupled receptor, it can also activate the Gq protein in certain contexts. For example, activation of the V2 receptor can lead to the release of IP3 and DAG, which can activate Gq-coupled receptors and lead to calcium mobilization in certain cell types.

Although lithium is known to primarily inhibit the Gq pathway by decreasing levels of IP3 and DAG, it can also affect the Gs pathway by inhibiting adenylate cyclase and decreasing cAMP levels. This can lead to decreased signaling through the V2 receptor and a reduction in water reabsorption in the kidney, which can contribute to some of the side effects of lithium therapy, such as nephrogenic diabetes insipidus. Therefore, while the V2 receptor is primarily a Gs protein-coupled receptor, its activation can also lead to the activation of the Gq pathway, and lithium can affect both pathways through its actions on intracellular signaling molecules.