Functional evidence for a role of GABA receptors in modulating nerve activities of circular smooth muscle from rat colon in vitro.
In the enteric nervous system, activation of neuronal GABA(A)- and GABA(B)-receptors has been shown to modulate neuronal activity. The consequences of this modulation depend on the location in the gastrointestinal tract or the animal species studied. These data illustrate the complexity of GABA-induced effects. Furthermore, the GABA(C)-receptor has been identified in a neuroendocrine cell line suggesting a modulating role of this third type of GABA receptor in intestinal functions. Therefore, the modulating role of GABA-receptor agonists was determined in circular preparations of rat distal colon during electrical nerve stimulation (NS) in vitro. Mechanical response to NS was characterized by a relaxation followed at the end of the stimulation by an off-contraction. In normal Krebs solution (basal conditions), muscimol and baclofen, respectively GABA(A)- and GABA(B)-agonists, induced a significant increase of the electrically induced off-contraction. The GABA(C) agonist, CACA, showed no significant effect on the response to NS. Excitatory effects of muscimol on the off-contraction were abolished in the presence of atropine. Furthermore, in the presence of atropine, muscimol increased the amplitude of the electrically induced relaxation; similarly the baclofen-induced increase of off-contraction amplitude was significantly lower than that observed in control conditions. Baclofen and muscimol effects on the off-contraction were abolished in the presence of hexamethonium or guanethidine. Furthermore, muscimol and baclofen did not induce any significant change on the response to NS in the presence of L-NAME and apamin together. Thus, it seems that in rat distal colon, GABA regulates significantly both excitatory (through GABA(A)- and GABA(B)-receptors) and inhibitory (through GABA(A)-receptors) neuronal activities. We also gave evidence for a possible interplay between GABAergic intrinsic neurons and adrenergic nerve terminals. Finally, it is shown for the first time the presence of the GABA vesicular transporter (VIAAT) around myenteric ganglia of rat colon.
Bayer
Sophie
S
INSERM Unit 338. Groupe de Neurogastroentérologie. Pavillon Poincaré. Hôpital Civil, 67000, Strasbourg, France.
Jellali
Abdeljalil
A
Crenner
Francis
F
Aunis
Dominique
D
Angel
Fabielle
F
D026905:Amino Acid Transport Systems; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009118:Muscimol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D018755:GABA Agonists; D018079:Receptors, GABA; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; D009118:Muscimol; D001418:Baclofen; D019331:NG-Nitroarginine Methyl Ester