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Substance P suppresses GABAA receptor function via protein kinase C in primary sensory neurones of bullfrogs.
Author(s) -
Yamada K,
Akasu T
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021697
Subject(s) - gabaa receptor , sensory system , receptor , neuroscience , function (biology) , protein kinase a , chemistry , substance p , microbiology and biotechnology , biology , kinase , medicine , biochemistry , neuropeptide
1. The effects of substance P (SP) and related tachykinins on the function of gamma‐aminobutyric acid‐A (GABAA) receptors were examined in acutely dissociated neurones of bullfrog dorsal root ganglia (DRG) by using whole‐cell voltage‐clamp techniques. 2. Application of SP (10 nM to 1 microM) depressed inward currents produced by GABAA receptor activation (IGABA). Neurokinin A (NKA) and neurokinin B (NKB) also depressed IGABA; the rank order of agonist potency was SP > NKA > NKB. Spantide ([D‐Arg1, D‐Trp7,9,Leu11]SP) and L‐703,606, NK1 receptor antagonists, blocked the SP‐induced depression of IGABA. 3. SP irreversibly depressed IGABA, when neurones were intracellularly dialysed with GTP gamma S. Intracellular application of GDP beta S prevented the SP‐induced depression of IGABA. Pertussis toxin (PTX) did not block the inhibitory effect of SP on IGABA. 4. The depression of IGABA produced by SP was inhibited by H‐7 and PKC(19‐36), protein kinase C (PKC) inhibitors, but not by H‐9 and HA‐1004, protein kinase A inhibitors. IGABA was suppressed by application of sn‐1,2‐dioctanoyl glycerol (DOG), a PKC activator. 5. It is concluded that activation of neurokinin‐1 (NK1) receptors downregulates the function of the GABAA receptor of primary sensory neurones through a PTX‐insensitive G‐protein. PKC may be involved in the transduction pathway of the tachykinin‐induced inhibition of the GABAA receptor.