PHARMACOLOGICAL CHARACTERISTICS OF EXCITATORY GAMMA-AMINOBUTYRIC-ACID(GABA) RECEPTORS IN A SNAIL NEURON

1. The pharmacologic characteristics of excitatory gamma-aminobutyric acid (GABA) receptors, termed muscimol II type GABA receptors, found i n a giant neuron type, v-LCDN (ventral-left cerebral distinct neuron), of an African giant snail (Achatina fulica Ferussac), were studied us ing the mammalian GABA receptor agonists, antagonists and synergists a nd GABA uptake inhibitor using the voltage clamp technique. 2. GABA an d its agonists, ejected by brief pressure, produced an inward current (I-in) of the following order of potency: trans-t-aminocrotonic acid ( TACA)>GABA>muscimol>isoguvacine>5-aminopentanoic acid and cis-4-aminoc rotonic acid (CACA). (+/-)-Baclofen and 3-aminopropylphosphonic acid ( APPA) were ineffective. The I-in values produced by GABA, TACA, isoguv acine and CACA were stable for at least 60 min, whereas the I-in induc ed by muscimol was not. 3. According to the dose-response curves of GA BA, TACA, isoguvacine and CACA, measured by the varied pressure durati on method, the ED(50) value of CACA was larger than those of the other compounds, and E(max) of TACh was larger than that of GABA, whereas E (max) values of isoguvacine and CACA were smaller. 4. The perfusion of beta-alanine, pentobarbital and 5-aminopentanoic acid inhibited the I -in induced by GABA, whereas (-)-bicuculline, pitrazepin, diazepam and 2-hydroxysaclofen had no effect. 5. From the effects of beta-alanine on the dose-response curves of GABA, measured by the varied pressure d uration method, beta-alanine competitively inhibited the I-in caused b y GABA. According to the effects of pentobarbital on the dose-response curves of GABA, this drug noncompetitively inhibited the I-in using t he varied pressure duration method, and partly competitively and partl y noncompetitively using the Y-tube method. The effects of 5-aminopent anoic acid on the dose-response curves of GABA indicated that this dru g noncompetitively inhibited the I-in using the varied pressure durati on method, and partly noncompetitively and partly uncompetitively usin g the Y-tube method. 6. The pharmacologic features of the Achatina mus cimol II type GABA receptors were similar to those of mammalian GABA(c ) (GABA(p1)) receptors, except for the effects of pentobarbital. Copyr ight (C) 1997 Elsevier Science Inc.