The role of GABA_A receptor function in peristaltic activity of the guinea‐pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin

Abstract

1 The peristaltic activity of the guinea-pig ileum was studied in the absence and in the presence of the blockade of GABAA receptors.2 Bicuculline (1-301pM), improved at the highest concentrations the efficiency of peristalsis by enhancing the frequency of propulsive contractions and the amount of fluid ejected per unit of time.3 Neither SR 95531 (0.3-101pM), a novel GABAA receptor antagonist, which competitively antagonized 3-aminopropane sulphonic acid induced contractions in myenteric plexus-longitudinal muscle preparations (pA2 value: 6.47), nor picrotoxinin (1-30pM) modified peristaltic parameters or influenced the potentiating effect of bicuculline on peristaltic activity. 4 In myenteric plexus-longitudinal muscle preparations, bicuculline (1-30 Mm) enhanced the amplitude of electrically-induced cholinergic contractions without modifying submaximal contractions to applied acetylcholine. SR 95531 and picrotoxinin had no effect on twitch amplitude. In the presence of each of these compounds, bicuculline retained its potentiating effect. 5 The results obtained with SR 95531 and picrotoxinin question the view that GABAA receptors may exert a critical role in intestinal propulsion by modulating the activity of nerve pathways subserving peristalsis. Bicuculline potentiates the peristaltic activity of the ileum probably via a facilitatory effect on enteric cholinergic transmission that is independent of GABAA receptor blockade.

An in vitro study of the relationship between GABA receptor function and propulsive motility in the distal colon of the rabbit

“…In our experiments, suppression of GABAA-receptor function by SR 95531, picrotoxinin or GABA desensitization was without effect on the velocity of propulsion, suggesting that GABAA-receptors are unlikely to have an important physiological role in rabbit colon peristalsis. These findings are in agreement with those recently obtained by our group in the guinea-pig ileum (Tonini et al, 1989). Direct stimulation of GABAA-receptors by 3-APS also failed to produce a consistent effect on peristaltic activity.…”

“…The inhibitory effect of GABA on propulsion was not with either of these antaj 10pM (Figure 7b). (Wermuth & Biziere, 1986) also effective at the intestinal level (Tonini et al, 1989). Relaxation was presumably due to stimulation of GABAA-receptors located on NANC inhibitory nerves.…”

“…The possible involvement of endogenous GABA in peristalsis was evaluated after suppression of GABA function by SR 95531, a novel competitive GABAA-receptor antagonist (Wermuth & Biziere, 1986;Tonini et al, 1989), or picrotoxinin (a blocker of the chloride channel associated with GABAA-receptors; Krantis & Kerr, 1981b), and in the presence of the non-specific GABAB-receptor antagonist D-aminovaleric acid (DAVA) (Muhyaddin et al, 1982;Ong & Kerr, 1987;Dickenson et al, 1988) (100pM) were also performed in the absence and in the presence of 10min exposure to the antagonists hyoscine, TTX, picrotoxinin and SR 95531. Any drug-induced change in 3-APS response was expressed as a % change with respect to the agonist basal response.…”

Impairment of GABA-Mediated Contractions of Rat Isolated Ileum by Experimental Diabetes

“…Although the concentrations required to observe the contractile effects of GABA and 3-APS in isolated rat ileum were of similar order as those reported for rat ileum [9] and guinea pig ileum myenteric plexuslongitudinal muscle preparations [10][11][12], the sensitivities to GABA and 3-APS were found to be lower in rat ileum (pD 2 4.74 B 0.03 and 4.52 B 0.06, respectively) than in guinea pig ileum (pD 2 5.03 B 0.09 and 5, respectively) [10,12]. The concentrations to produce the maximal effect of these agents in rat ileum were about 5-10 times higher than those reported for the maximal effects in guinea pig ileum [10][11][12].…”

“…Although the concentrations required to observe the contractile effects of GABA and 3-APS in isolated rat ileum were of similar order as those reported for rat ileum [9] and guinea pig ileum myenteric plexuslongitudinal muscle preparations [10][11][12], the sensitivities to GABA and 3-APS were found to be lower in rat ileum (pD 2 4.74 B 0.03 and 4.52 B 0.06, respectively) than in guinea pig ileum (pD 2 5.03 B 0.09 and 5, respectively) [10,12]. The concentrations to produce the maximal effect of these agents in rat ileum were about 5-10 times higher than those reported for the maximal effects in guinea pig ileum [10][11][12]. However, it is not known whether there is a difference between rat and guinea pig ileal tissues in terms of maximal responses to GABA and 3-APS, since we expressed contractile force as milligrams of developed tension per milligram of tissue weight, whereas these authors expressed their data as either gram tension [10] or percent of maximal response [11,12].…”