Acid secretagogue action of structurally gamma-aminobutyric acid(GABA)-related compounds in rats.

Yamasaki, K.; Gotō, Yoshiaki

doi:10.1254/jjp.52.255

Cited by 6 publications

(8 citation statements)

References 28 publications

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“…The vagal efferent response to PCPGABA at the dose of 4 mg/kg, s.c. preceded gastric acid secretion. The acid secretagogue response to PCPGABA was more potent than that in response to histamine or bethanechol (9). Muscimol, an agonist acting selectively at bicuculline-sensitive GABAA receptor sites (25), also caused an activation in vagal efferent transmission more rapidly than PCPGABA, followed by gastric hypersecretion which is in accordance with previous findings using pylorus ligated rats (26).…”

Section: Discussionsupporting

confidence: 91%

“…The pathological mechanisms of stress ulceration nave otten been attnbuted to gastric hypersecretion (21)(22)(23). Pharmacological studies of brain neurotransmitters suggest that central GABAergic mechanisms are involved in the stimulation of gastric acid secretion in several species (7)(8)(9)(10)(11) and also participate in the aggravation of stress-induced ulceration.…”

Section: Discussionmentioning

confidence: 99%

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GABAA and GABAB-receptor agonists evoked vagal nerve efferent transmission in the rat.

Yamasaki

Gotō

Hara³

et al. 1991

Jpn.J.Pharmacol

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ABSTRACT-The effect of GABA agonists on vagal efferent activity was studied in anesthetized rats. PCPGABA, a GABAB agonist (4 and 8 mg/kg, s.c.), markedly activated the neural efferent discharge of the vagus. Muscimol, a GABAA agonist (0.1 and 0.3 mg/kg, i.v.), also facilitated vagal activity. Both agonists caused significant gastric acid hyperacidity. Bicuculline (0.25 mg/kg, i.v.) or picrotoxin (0.5 mg/kg, i.v.) given 10 min prior to each agonist had no effect on the frequency of vagal nerve firing elicited by PCPGABA (4 mg/kg, s.c.) or muscimol (0.3 mg/kg, i.v.). Pretreatment with scopolamine (0.25 mg/kg, i.v.) abolished PCPGABA stimulated vagal activity and gastric acid secretion. Methscopolamine (0.25 mg/kg, i.v.) inhibited only the hyperacidity evoked by PCPGABA, but not vagal activation. These results suggest that PCPGABA and muscimol may cause gastric acid secretion through central cholinergic descending mechanisms that are resistant to GABAA and GABAB antagonists.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

GABAA and GABAB-receptor agonists evoked vagal nerve efferent transmission in the rat.

Yamasaki

Gotō

Hara³

et al. 1991

Jpn.J.Pharmacol

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“…y-Aminobutyric acid (GABA)-mimetics injected sys temically have been shown to produce significant in creases in gastric acid secretion in a number of species including rats (1, 2), dogs (3) and humans (4); and these secretagogue effects were totally abolished by truncal vagotomy and atropine (1,2). Moreover GABA at acid secretagogue doses caused a marked activation of vagal efferent discharges at the cervical level (1).…”

mentioning

confidence: 99%

“…We have recently shown that certain GABA mimetic ligands such as isoguvacine, a GABAA agonist, and 5 aminovaleric acid, a weak GABAA agonist and a GABAB antagonist, also stimulate gastric secretion with a potency similar to or greater than that of GABA (2). Baclofen seems to be one of the most potent in stimulating gastric secretion (2).…”

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confidence: 99%

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.BETA.-Phenyl-.BETA.-Alanine Prevents the Activation of Vagal Efferent Discharges Evoked by Baclofen and GABA in Rats.

Yamasaki

Gotō

1992

Jpn.J.Pharmacol

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ABSTRACT-The effects of DL-fl-phenyl-,8-alanine (BPBA) on vagal efferent discharges elicited by y aminobutyric acid (GABA) and baclofen were investigated in rats. When given alone, BPBA (40 mg/kg, i.v.) caused no significant change in vagal nerve response and did not elicit any convulsions. Pretreatment with BPBA (40 mg/kg, i.v.) resulted in 70% and 80% reductions in the vagal efferent dis charges induced by GABA (400 mg/kg, i.v.) and baclofen (4 mg/kg, s.c.), respectively. The present re sults suggest that BPBA may be a novel GABA antagonist with respect to vagal activation mechanisms in the CNS.Keywords: GABA, Baclofen,,8-Phenyl-/3-alanine (BPBA) y-Aminobutyric acid (GABA)-mimetics injected sys temically have been shown to produce significant in creases in gastric acid secretion in a number of species including rats (1, 2), dogs (3) and humans (4); and these secretagogue effects were totally abolished by truncal vagotomy and atropine (1, 2). Moreover GABA at acid secretagogue doses caused a marked activation of vagal efferent discharges at the cervical level (1). Although GABA actions in the CNS are strongly impli cated in these effects, until now, the underlying mechanisms, including receptor subtypes, have been unclear (5).Intravenous administration of DL-/9-phenyl-,8-alanine (BPBA) has recently been shown to prevent baclofen induced gastric acid secretion without altering the re sponse to bethanechol in stomach perfused rat (6, 7). However, the general pharmacodynamic profile of BPBA is poorly described. Studies employing the moni toring of vagal efferent discharges are important for de termining the site of the blocking effect of BPBA with respect to gastric acid secretion, whether it be in the periphery or at a central site. Therefore the aim of the present study was to determine whether the systemic administration of BPBA could prevent the baclofen induced activation of vagal efferent discharges recorded at the cervical level and whether such antagonism by BPBA is specific for baclofen or not.Adult male Wistar/ST-strain rats weighing 180 220 g were used in this experiment. They were housed in a controlled environment, exposed to a 12-hr light-dark cycle and fed with standard rodent chow and water ad libitum for at least 1 week before initiation of the ex periment. Rats were fasted for at least 18 hr prior to each experiment but allowed free access to water.Rats were anesthetized with urethane (1.25 g/kg, i.p.). The cervical skin was incised, and a tracheotomy was performed, followed by exposure of the vagal trunks. The cavity was then filled with warm paraffin. The left vagus nerve was mounted on a bipolar plati num electrode for recording vagal efferent activity. The peripheral portion of the nerve was crushed to exclude the possibility of contamination by input of afferent dis charges. Using a biophysical amplifier, the neural activ ity was displayed on an oscilloscope and averaged with a window discriminator, which could distinguish im pulses of efferent discharges from background noise. The rate of f...

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γ-Aminobutyric acid and gastric acid secretion: A physiologic role?

Thirlby

Pleis

1991

Journal of Surgical Research

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Acid secretagogue action of structurally gamma-aminobutyric acid(GABA)-related compounds in rats.

Abstract: Abstract-Theproperties of GABA related compounds on gastric function were studied in standardized perfused rat stomach preparations.

Cited by 6 publications

References 28 publications

GABAA and GABAB-receptor agonists evoked vagal nerve efferent transmission in the rat.

GABAA and GABAB-receptor agonists evoked vagal nerve efferent transmission in the rat.

.BETA.-Phenyl-.BETA.-Alanine Prevents the Activation of Vagal Efferent Discharges Evoked by Baclofen and GABA in Rats.

γ-Aminobutyric acid and gastric acid secretion: A physiologic role?

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