Differential G protein-mediated coupling of neurotransmitter receptors to Ca²⁺ channels in rat dorsal root ganglion neurons in vitro

The peptides neuropeptide Y (NPY) and bradykinin (BK) both inhibited Ca²⁺ currents in rat dorsal root ganglion neurons (DRG) in vitro. The effects of both peptides were completely blocked by treatment of cells with pertussis toxin. Based on antigenic determinants, DRG cells contained at least two pertussis toxin substrates, α_o (M_r, 39kd) and α_i2 (M_r 40 kd). We examined the ability of three purified bovine α subunits (identified with antibodies as α_o, α₁, and α₂) to reconstitute the inhibitory effects of NPY and BK. Reconstitution of NPY effects occurred according to the potency series α_o>α_i1≫α_i2. However, in the case of BK all three G proteins were approximately equally effective. Whereas complete reconstitution of NPY effects could be obtained with α_o, no single a subunit produced complete reconstitution of BK. Combinations of α_o and α_i2, however, were able to completely reconstitute the effects of BK. Thus several G proteins can effect the regulation of Ca²⁺ channels in these cells. However, neurotransmitters may be selective in the G proteins or combinations of G proteins utilized to achieve this regulation.