Excitatory and inhibitory responses mediated by GABAA and GABAB receptors in guinea pig distal colon.
The actions of gamma-aminobutyric acid (GABA) and the receptor selective agonists, muscimol (GABAA) and baclofen (GABAB), on motor activity of the longitudinal muscle-myenteric plexus of guinea-pig distal colon were studied in vitro. Preparations exhibited spontaneous contractions that were blocked by scopolamine (1 microM) or tetrodotoxin (1 microM). GABA (3-100 microM) inhibited these contractions; the EC50 was 8 microM. GABA-induced relaxations were not blocked by picrotoxin (30 microM). The GABAA receptor antagonist, bicuculline (3-30 microM), increased the amplitude of spontaneous contractions; this response was not blocked by tetrodotoxin. Baclofen (3-100 microM; EC50 = 14 microM) mimicked the GABA-induced relaxation. Baclofen-induced relaxations were not blocked by the GABAB antagonist, phaclofen (30-100 microM). Muscimol (10-100 microM) induced a contraction followed by a relaxation; both responses faded in the presence of muscimol. The muscimol EC50's for contraction and relaxation were 12.5 and 11 microM, respectively. The muscimol contraction was blocked by tetrodotoxin, scopolamine and picrotoxin and was reduced by hexamethonium (30 microM). Muscimol relaxations were blocked by tetrodotoxin, picrotoxin and apamin (0.1 microM). Muscimol responses were not altered after preincubation of the tissues with cortisol (10 pM-1 microM). These data indicate that GABA can act at presynaptic GABAB receptors to inhibit acetylcholine release from enteric neurons and reduce spontaneous contractions. There are also GABAA receptors on excitatory and inhibitory neurons and agonist action at these receptors results in contraction and relaxation.
Department of Internal Medicine, Michigan State University, East Lansing 48824.
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Minocha
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Galligan
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009599:Nitroprusside / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D009599:Nitroprusside; D009118:Muscimol; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen