A facilitatory effect of bicuculline on the enteric neurones in the guinea‐pig isolated colon

Abstract

Changes in the efficiency of the peristaltic reflex, acetylcholine (ACh) output and motor responses to transmural and periarterial nerve stimulation produced by bicuculline and -y-aminobutyric acid (GABA) receptor desensitization were investigated in the guinea-pig isolated colon. 2 Bicuculline, at concentrations unable to affect spontaneous colonic motility and lacking anticholinesterase activity, produced a dose-dependent increase of both the efficiency of the peristaltic reflex and the stimulated ACh output. Such effects could not be observed in GABA-desensitized preparations. 3 A frequency-dependent potentiation of the cholinergic excitatory and non-adrenergic noncholinergic (NANC) inhibitory responses to transmural stimulation was also observed in the presence of bicuculline. Conversely bicuculline exhibited an inhibitory effect on the relaxation induced by periarterial nerve stimulation. 4 Acute GABA-desensitization was unable to affect the contractile responses to transmural stimulation, the ACh output and the efficiency of the peristaltic reflex. On the contrary, desensitization was able to mimic the effects of bicuculline on the inhibitory responses to both transmural and periarterial nerve stimulation. 5 Our results are consistent with a significant role played by an intrinsic GABAergic pathway in the modulation of both cholinergic excitatory and NANC inhibitory neurones. The hypothesis is advanced that a feed-back modulation carried out through bicuculline-sensitive GABAergic synapses could operate during the propagation of peristaltic motor activity.

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

“…guinea-pig) was previously investigated in the presence of GABA desensitization or GABAA-receptor antagonists. The results, however, were conflicting since endogenous GABA was found not to be involved in peristaltic reflexes (Krantis et al, 1980) or to induce both excitatory (Krantis & Kerr, 1981a;Ong & Kerr, 1983) or inhibitory effects (Frigo et al, 1987) on propulsion, via an effect on GABAA-receptors. 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.…”

“…Studies designed to evaluate the possible functional role of GABA-containing neurones on the propulsive activity of guinea-pig colon by using GABAA-receptor antagonists and desensitization procedures have given conflicting results. In fact, GABAA-receptors were considered not to be involved in the modulation of distension-initiated enteric reflexes (Krantis et al, 1980), to reduce (Frigo et al, 1987), or, together with GABAB-receptors (Ong & Kerr, 1983) to enhance the efficiency of peristalsis (Krantis & Kerr, 1981a).…”

Circadian Phase Shifts to Neuropeptide YIn Vitro: Cellular Communication and Signal Transduction

“…This would suggest that effects reported in earlier in vivo studies (Huhman et al, 1995) may be the result of a nonspecific action by millimolar concentrations of Bic. For instance, at high concentrations Bic can inhibit acetylcholinesterase activity (Frigo et al, 1987), may depolarize neurons by blocking a potassium conductance (Heyer et al, 1982), and can have other nonspecific effects (Bartolini et al, 1990). TTX (1 M) blocks most I PSC s but does not block spontaneous EPSC s in SC N brain slices (Jiang et al, 1995a).…”

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

“…Bicuculline, in spite of being not completely devoid of non-specific effects (Bartolini et al, 1985), has been commonly (and often solely) employed to evaluate the role of GABAA receptor function on intestinal peristalsis. In the guinea-pig isolated colon, bicuculline has been shown either to increase (Frigo et al, 1987) or to inhibit (Krantis & Kerr, 1981b) peristaltic activity and to be ineffective in modifying both the excitatory and inhibitory reflexes subserving peristalsis (Krantis et al, 1980). Recently, the facilitatory effect of bicuculline on ileal propulsive activity has been explained by assuming an involvement of endogenous GABA in the inhibition of the peristaltic reflex, possibly via GABAA receptors located on inhibitory nonadrenergic, non-cholinergic (NANC) nerve pathways (Schworer & Kilbinger, 1988 hypothesis is questionable because in the guinea-pig ileum activation of GABAA receptors is associated with excitation of cholinergic nerves (Krantis & Kerr, 1981a;Kaplita et al, 1982;Giotti et al, 1983;Kleinrok & Kilbinger, 1983;Taniyama et al, 1983;Tonini et al, 1987) (Kaplita et al, 1982;Giotti et al, 1983;Kleinrok & Kilbinger, 1983;Cherubini & North, 1984a;Ong et al, 1987).…”

“…This is probably the mechanism through which applied GABA inhibits propulsive activity in the guinea-pig ileum (Hobbiger, 1958;Inouye et al, 1960 In an attempt to understand the facilitatory effect of bicuculline on peristalsis, we have re-assessed the effect of this compound on cholinergic transmission since bicuculline, at least in the central nervous system, is endowed with some 'cholinergic activity' partly related to acetylcholinesterase inhibition (Gardner & Webster, 1973;Svenneby & Roberts, 1974;Breuker & Johnston, 1975). In the intestine, a bicuculline-induced facilitatory effect on ACh release (at concentrations having no anticholinesterase activity) has been demonstrated only in the guineapig colon (Frigo et al, 1987). In contrast, a number of studies have indicated that bicuculline (10m) fails to modify ACh release (Kleinrok & Kilbinger, 1983) and electrically-induced cholinergic contractions (Krantis & Kerr, 198 la;Allan & Dickenson, 1986) in the small intestine of the same animal species.…”