Neurokinin-1 (NK₁) Receptors Mediate Tachykinin-Induced Depression of GABA Current in Bullfrog Sensory Neurons

Abstract

Receptors responsible for the tachykinin-induced depression of γ-aminobutyric acid-A (GABA_A) receptors in neurons of bullfrog dorsal root ganglia (DRG) were investigated by using whole-cell voltage-clamp techniques. Substance P (10 nM-1 μM) depressed the inward current produced by GABA (GABA current) in a concentration-dependent manner . Substance P did not change the reversal potential of the GABA current. Neurokinin A also depressed the GABA current with potency similar to those of substance P. [D-Arg¹, D-Trp^{7, 9} Leu¹¹]substance P (spantide, 1 μM) shifted the concentration-inhibition curve of substance P to the right. Spantide (1 μM) increased the IC₅₀ from 56 nM to 210 nM. Lineweaver-Burk plot, a reciprocal plot of the concentration-inhibition curve, showed that spantide did not change the maximum response (V^max) to substance P but increased the apparent dissociation constant (K_d). CP99994 (1 μM), an neurokinin-1 (NK₁) receptor antagonist, inhibited the substance P-induced depression of the GABA current. These results suggest that the tachykinin-induced depression of the GABA_A receptor sensitivity is mediated by NK₁ receptors in neurons of bullfrog DRG.