Effects of GABA on circular smooth muscle spontaneous activities of rat distal colon.
GABAergic regulation of intestinal motility through the modulation of non-adrenergic non-cholinergic (NANC) neurons remains poorly understood especially in rat colon where very few studies have been undertaken. Therefore, the effects of GABA on circular preparations of rat distal colon were investigated using classical organ bath chambers to record spontaneous mechanical activities (SMA). SMA was characterized by the occurrence of rhythmic phasic contractions (type-I) or by spontaneously occurring large contractions superimposed on small rhythmic contractions (type-II). In the presence of atropine and guanethidine (NANC conditions), these large contractions were inhibited by bicuculline, a GABA(A)-receptor antagonist as well as by TTX, L-NAME and apamin together, or L 732-138, a NK1-receptor antagonist. In NANC conditions, GABA induced a transient monophasic relaxation or a biphasic effect characterized by a relaxation followed by a tonic contraction in both type-I and -II preparations. Both the inhibitory and excitatory effects of GABA were blocked by TTX and L-NAME + apamin; the GABA-induced contraction was also sensitive to L 732-138. The responses to GABA were mimicked by the GABA(A)-receptor agonist, muscimol, whereas baclofen and CACA, respectively GABA(B) and GABA(C)-receptors agonists showed no effect. These results demonstrated that only GABA(A)-receptors seem to be involved in the regulation of SMA in rat distal colon in NANC conditions. Release of NANC inhibitory transmitter (NO and probably ATP) and NANC excitatory transmitter (maybe substance P) might be involved.
Bayer
S
S
INSERM Unité 338. Groupe de Neurogastroentérologie. Pavillon Poincaré. Hôpital Civil. 67000 Strasbourg, France.
Crenner
F
F
Aunis
D
D
Angel
F
F
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D013565:Sympatholytics; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine