Abstract
Receptors responsible for the tachykinin-induced depression of gamma-aminobutyric acid-A (GABAA) receptors in neurons of bullfrog dorsal root ganglia (DRG) were investigated by using whole-cell voltage-clamp techniques. Substance P (10 nM-1 microM) 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-Trp7,9, Leu11]substance P (spantide, 1 microM) shifted the concentration-inhibition curve of substance P to the right. Spantide (1 microM) 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 (Vmax) to substance P but increased the apparent dissociation constant (Kd). CP99994 (1 microM), 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 GABAA receptor sensitivity is mediated by NK1 receptors in neurons of bullfrog DRG.
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