Figure 1.

Suggested Ca²⁺ signal transduction pathways induced by 3-iodothyronamine (3-T₁AM). Two G protein-coupled receptors (GPCRs), known as trace amine-associated receptor 1 (TAAR1) and β-adrenergic receptors, can be activated and one GPCR known as muscarinic type 3 receptor can be suppressed by 3-T₁AM. 3-T₁AM increases [Ca²⁺]_i via a member of the transient receptor channel superfamily known as transient receptor potential channel melastatin 8 (TRPM8) (menthol or cold receptor), and this effect is blocked by BCTC. 3-T₁AM may either directly activate TRPM8 by a GPCR-independent mechanism or indirectly via the β/γ-subunits of Gi/o downstream of β-adrenergic receptors. TRPM8 activation by 3-T₁AM inhibits TRPV1 (capsaicin or heat receptor)-induced Ca²⁺ influx. Notably, 3-T₁AM may also directly suppress TRPV1 by a GPCR-independent mechanism (↓[Ca²⁺]_i). So far, the involvement of other GPCRs and TRPs in 3-T₁AM-induced signaling effects remained elusive.