Neurokinin-1 (NK1) receptors mediate tachykinin-induced depression of GABA current in bullfrog sensory neurons.
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.
Akasu
T
T
Department of Physiology, Kurume University School of Medicine, Japan.
Yamada
K
K
D000818:Animals; D003864:Depression, Chemical; D015536:Down-Regulation; D009475:Neurons, Afferent / Q000187:drug effects*; D011892:Rana catesbeiana; D011963:Receptors, GABA-A / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D011963:Receptors, GABA-A; D018040:Receptors, Neurokinin-1; D013373:Substance P