EFFECTS OF INHIBITORS FOR INTRACELLULAR SIGNAL-TRANSDUCTION SYSTEMS ON THE INWARD CURRENT PRODUCED BY GABA IN A SNAIL NEURON

1. An inward current (I-in) was produced by gamma-aminobutyric acid (G ABA) and muscimol, but not by baclofen, in an identifiable giant neuro n type, V-LCDN (ventral left cerebral distinct neuron), of an African giant snail (Achatina fulica Ferussac) under voltage clamp. 2. The pha rmacological features of the excitatory GABA receptors in this Achatin a neuron type, termed the Achatina muscimol II type GABA receptors, we re mainly comparable to those of the mammalian GABA(C) receptors. 3. I t was demonstrated in the present study that the following inhibitors for intracellular signal transduction systems showed no significant ef fect on the I-in produced by GABA in this Achatina neurontype: H-7 [1- (5-isoquinolinylsulfonyl)-2-methylpiperazine], an inhibitor of cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinas e (PKG) and protein kinase C (PKC); H-8 (N-[2-(methylamino) ethyl]-5-i soquinolinesulfonamide), a PKA and PKG inhibitor; H-9[N-(2-aminoethyl) -5-isoquinolinesulfonamide], a PKA inhibitor; staurosporine ((9 alpha, 10 beta,11 beta,13 alpha)-(+)-2,3,10,11,12,13-hexahydro (methylamino)- 9,13-epoxy-1H,9H-diindolo[1,2,3,-gh: 3',2',1'-1m]pyrrolo[3,4-j] [1,7]b enzodiazonin-1-one), a PKA and PKC inhibitor; KT5823 ((8R,9S,11S)-9-me thoxy-9-methoxycarbonyl- triazadibenzo[a,g]cycloocta[c,d,e]-trinden-1- one), a PKG inhibitor; (6-aminohexyl)-5-chloro-1-naphthalenesulfonamid e], a calmodulin inhibitor; ML-9 onaphthalene-1-sulfonyl-1H-hexahydro- 1,4-diazepine hydrochloride], a myosin light chain kinase inhibitor; g enistein ydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one], a tyrosine protein kinase inhibitor; IBMX (3-isobutyl-1-methylxanthine), a cycli c nucleotide phosphodiesterase (PDE) inhibitor; fluphenazine nitrogen mustard ifluoromethyl-10-phenothiazinyl)-propyl]piperazine dihydrochlo ride), a calmodulin-dependent PDE inhibitor; calyculin A, a type 1 pro tein phosphatase inhibitor; and okadaic acid (9,10-deepithio-9,10-dide hydroacanthifolicin), a type 1, 2A and 2B protein phosphatase inhibito r. 4. With these results, it was proposed that the excitatory Achatina muscimol II type GABA receptors in v-LCDN are not metabotropic but io notropic. (C) 1998 Elsevier Science Inc.