Summary
We investigated the effect of GABA on the spontaneous efflux of 3H-acetylcholine (ACh) from the isolated guinea pig gallbladder loaded with 3H-choline. Application of GABA (10−5 M) caused a significant increase in the fractional rate of tritium efflux. This GABA-evoked efflux of ACh was inhibited by the perfusion of tetrodotoxin (10−6 M) and Ca-free medium. Nipecotic acid (10−4 M) did not affect the GABA-evoked release of ACh, indicating that ACh was not released by the entry of GABA into cholinergic nerve terminals. Bicuculline (10−6 M) and furosemide (10−6 M), the chloride ion channel blocker, inhibited the GABA-evoked ACh release. The application of muscimol (10−5 M), but not baclofen (10−5 M) also produced an increase in the fractional rate of ACh release. Thus, the GABA receptors involved in the increase of ACh release are bicuculline-sensitive. The GABA-evoked release of ACh was not altered by the perfusion with hexamethonium (10−5 M), thus indicating the presence of GABA receptors on the postganglionic cholinergic neurons.
These findings suggest that bicuculline-sensitive GABA receptors probably coupled to a Cl− ionophore are present on postganglionic cholinergic neurons and are involved in the increase of ACh release in guinea pig gallbladder.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bowery NG, Jones GP, Neal MJ (1976) Selective inhibition of neuronal GABA uptake by cis-1,3-aminocyclohexane carboxylic acid. Nature 264:281–284
Bowery NG, Hill DR, Hudson L, Doble A, Middlemis DN, Shaw J, Turnbull M (1980) (−)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptors. Nature 283:92–94
Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ, Warrington R (1981) Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol 71:53–70
Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983) GABAA and GABAB receptor-mediated effects in guinea pig ileum. Br J Pharmacol 78:467–478
Johnston GAR (1976) Physiologic pharmacology of GABA and its antagonists in the vertebrate nervous system. In: Roberts E, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York, pp 395–411
Kaplita PV, Waters DH, Triggle DJ (1982) γ-Aminobutyric acid action in guinea pig ileal myenteric plexus. Eur J Pharmacol 79:43–51
Kleinrok A, Kilbinger H (1983) γ-Aminobutyric acid and cholinergic transmission in the guinea pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 322:216–220
Krantis A, Costa M, Furness JB, Orbach J (1980) γ-Aminobutyric acid stimulates intrinsic inhibitory and excitatory nerves in the guinea pig intestine. Eur J Pharmacol 67:461–468
Krantis A, Kerr DIB (1981) GABA induced excitatory responses in the guinea pig small intestine are antagonized by bicuculline, picrotoxin and chloride ion blockers. Naunyn-Schmiedeberg's Arch Pharmacol 317:257–261
Krnjevic K (1976) Inhibitory action of GABA and GABA-mimetics on vertebrate neurons. In: Roberts E, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York, pp 269–281
Krogsgaard-Larsen P, Johnston GAR (1975) Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J Neurochem 25:797–802
Mayer CJ, Camerer H, Dembowsky K, Grafe P, Steiger A (1982) Actions of amino-acid neurotransmitter on myenteric neurons. In: Weinbeck M (ed) Motility of the digestive tract. Raven Press, New York, pp 103–108
Narahashi T (1974) Chemicals as tools in the study of excitable membranes. Physiol Rev 54:813–889
Nicholl RA (1978) The blockade of GABA mediated responses in the frog spinal cord by ammonium ions and furosemide. J Physiol 283:121–132
Olsen RW (1981) The GABA postsynaptic membrane receptor-ionophore complex. Mol Cell Biochem 39:261–279
Ong J, Kerr DIB (1983) GABAA- and GABAB-receptor mediated modification of intestinal motility. Eur J Pharmacol 86:9–17
Reimann W, Zumstein A, Starke K (1982) γ-Aminobutyric acid can both inhibit and facilitate dopamine release in the caudate nucleus of the rabbit. J Neurochem 39:961–969
Rubin RP (1970) The role of calcium in the release of neurotransmitter substances and hormones. Pharmacol Rev 22:389–428
Schousboe A, Thorbeck P, Hertz L, Krogsgaard-Larsen P (1979) Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding. J Neurochem 33:181–189
Szerb JC (1976) Storage and release of labelled acetylcholine in the myenteric plexus of the guinea pig ileum. Can J Physiol Pharmacol 54:12–22
Taniyama K, Kusunoki M, Saito N, Tanaka C (1982) Release of γ-aminobutyric acid from cat colon. Science 217:1038–1040
Taniyama K, Kusunoki M, Saito N, Tanaka C (1983) GABA evoked ACh release from isolated guinea pig ileum. Life Sci 32:2349–2353
Author information
Authors and Affiliations
Additional information
This paper is part of a dissertation submitted by N. Saito to Kobe University School of Medicine, for the requirement of Doctor of Philosophy
Rights and permissions
About this article
Cite this article
Saito, N., Taniyama, K. & Tanaka, C. 3H-ACh release from guinea pig gallbladder evoked by GABA through the bicuculline-sensitive GABA receptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 45–48 (1984). https://doi.org/10.1007/BF00518777
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00518777