Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons.
The effects of tachykinins on primary afferent neurons of bullfrog dorsal root ganglia (DRG) were examined by using whole-cell patch-clamp methods. Neurokinin A (NKA) caused inward current (INKA) in a concentration-dependent manner. Concentration-response curve showed that the EC50 for NKA was 6 nM. The INKA showed strong tachyphylaxis, when NKA was continuously applied for more than 1 min. Substance P (SP) also produced inward current with potency similar to that of NKA. Neurokinin B (NKB) was less effective in producing the inward current. The order of agonist potency was NKA = SP >> NKB. Spantide ([D-Arg1, D-Trp7.9, Leu11]SP), a non-selective peptide antagonist at tachykinin receptors, 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 INKA was associated with decrease in K+ conductance. NKA suppressed both a voltage-dependent K+ current, the M-current (IM), and a voltage-independent background K+ current, IK(B). Intracellular dialysis with GTP gamma S (100 nM) or GDP beta S (100 microM) depressed the INKA. Pre-treatment of DRG neurons with pertussis toxin (PTX) did not prevent the INKA. Depletion of intracellular ATP depressed the INKA. 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.
Akasu
T
T
Department of Physiology, Kurume University School of Medicine, Japan.
Ishimatsu
M
M
Yamada
K
K
D000818:Animals; D001464:Barium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011892:Rana catesbeiana; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D015320:Tachykinins / Q000494:pharmacology*
D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D001464:Barium; D011188:Potassium