TACHYKININS CAUSE INWARD CURRENT THROUGH NK1 RECEPTORS IN BULLFROG SENSORY NEURONS

The effects of tachykinins on primary afferent neurons of bullfrog dor sal root ganglia (DRG) were examined by using whole-cell patch-clamp m ethods. Neurokinin A (NKA) caused inward current (I-NKA) in a concentr ation-dependent manner. Concentration-response curve showed that the E C(50) for NKA was 6 nM. The I-NKA showed strong tachyphylaxis, when NK A was continuously applied for more than 1 min. Substance P (SP) also produced inward current with potency similar to that of NKA. Neurokini n B (NKB) was less effective in producing the inward current. The orde r of agonist potency was NKA = SP >> NKB. Spantide ([D-Arg(1), D-Trp(7 ,9), Leu(11)]SP), a non-selective peptide antagonist at tachykinin rec eptors, reduced the tachykinin-induced current. CP-99,994, a selective non-peptide antagonist for neurokinin-1 (NK1) receptor, inhibited the inward currents produced by NKA and SP. The I-NKA was associated with decrease in K+ conductance. NKA suppressed both a voltage-dependent K + current, the M-current (I-M), and a voltage-independent background K + current, I-K(B). Intracellular dialysis with GTP gamma S (100 nM) or GDP beta S (100 mu M) depressed the I-NKA. Pre-treatment of DRG neuro ns with pertussis toxin (PTX) did not prevent the I-NKA. Depletion of intracellular ATP depressed the I-NKA. These results suggest that the tachykinin-induced inward current is mediated through the NK1 receptor which mainly couples to PTX-insensitive G-protein in bullfrog primary afferent neurons.