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

Yamasaki, K.; Gotō, Yoshiaki; Hara, Nobuyuki; Hara, Youichi

doi:10.1254/jjp.55.11

Cited by 7 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior to determining the presence of the proposed parallel “dual effector” pathways (NANC and cholinergic) in the DMN (Andrews et al, 1987; Yamasaki et al, 1991; Lloyd et al, 1993; Rogers et al, 1999, 2003; Browning and Travagli, 2001; Lewis et al, 2002; Holmes et al, 2013) using baclofen, we first chose to determine if the drug’s effect on IGP was mediated by the vagus nerve. To this end, 7.5 pmol baclofen was microinjected into the DMV before and after ipsilateral vagotomy.…”

Section: Resultsmentioning

confidence: 99%

“…However, if this were the predominant case, and assuming that ongoing activity of these DMV neurons results in the discharge of preganglionic vagal cholinergic nerves innervating gastric smooth muscle, the outcome of a postsynaptic inhibitory action in vivo would be a decrease in vagal nerve discharge. Instead, the opposite occurs as baclofen given systemically increases the vagus nerve discharge (Goto et al, 1985; Yamasaki et al, 1991). While Browning and Travagli (2001) accept the findings that baclofen given systemically increases gastric motility and tone; however, they attribute these effects to the postsynaptic inhibition of DMV neurons that provide an inhibitory drive (i.e., ‘NANC drive’) to the stomach.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

GABAB Receptor Signaling in the Dorsal Motor Nucleus of the Vagus Stimulates Gastric Motility via a Cholinergic Pathway

et al. 2019

View full text Add to dashboard Cite

Central nervous system regulation of the gastric tone and motility is primarily mediated via preganglionic neurons of the dorsal motor nucleus of the vagus (DMV). This is thought to occur by simultaneous engagement of both independent excitatory and inhibitory pathways from the DMV and has been proposed to underlie the opposing effects seen on gastric tone and motility in a number of in vivo models. Contrary to this view, we have been unable to find any evidence for this “dual effector” pathway. Since this possibility is so fundamental to how the brain-gut axis may interact in light of both peripheral and central demands, we decided to explore it further in two separate animal models previously used in conjunction with GABAB signaling to report the existence of a “dual effector” pathway. Using anesthetized rats or ferrets, we microinjected baclofen (7.5 pmol; n = 6), a GABAB agonist into the DMV of rats or intravenously administered it (0.5 mg/kg; n = 4) in ferrets. In rats, unilateral microinjection of baclofen into the DMV caused a robust dose-dependent increase in gastric tone and motility that was abolished by ipsilateral vagotomy and counteracted by pretreatment with atropine (0.1 mg/kg; IV). Similarly, as microinjection in the rats, IV administration of baclofen (0.5 mg/kg) in the ferrets induced its characteristic excitatory effects on gastric tone and motility, which were blocked by either pre- or post-treatment with atropine (0.1 mg/kg; IV). Altogether, our data provide evidence that the gastric musculature (other than the gastric sphincters) is regulated by a “single effector” DMV pathway using acetylcholine.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GABAB Receptor Signaling in the Dorsal Motor Nucleus of the Vagus Stimulates Gastric Motility via a Cholinergic Pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In keeping with such a hypothesis baclofen, or the GABA mimetic PCP-GABA, induce an increase in gastric acid secretion beyond that induced by histamine and cholinergic agonism alone (Goto and Debas, 1983). This effect occurs independently of GABA A receptors (Hara et al, 1990; Yamasaki et al, 1991) and is accompanied by an increase in vagal cholinergic outflow (Yamasaki et al, 1991). Consistent with such a vagal-cholinergic pathway, systemic baclofen-induced acid secretion (and gastric motility) was inhibited by both atropine and vagotomy (Andrews and Wood, 1986).…”

Section: Gabab Receptors and Gastrointestinal Functionmentioning

confidence: 99%

A Gut Feeling about GABA: Focus on GABAB Receptors

Hyland¹,

Cryan²

2010

Front. Pharmacol.

158

121

View full text Add to dashboard Cite

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the body and hence GABA-mediated neurotransmission regulates many physiological functions, including those in the gastrointestinal (GI) tract. GABA is located throughout the GI tract and is found in enteric nerves as well as in endocrine-like cells, implicating GABA as both a neurotransmitter and an endocrine mediator influencing GI function. GABA mediates its effects via GABA receptors which are either ionotropic GABAA or metabotropic GABAB. The latter which respond to the agonist baclofen have been least characterized, however accumulating data suggest that they play a key role in GI function in health and disease. Like GABA, GABAB receptors have been detected throughout the gut of several species in the enteric nervous system, muscle, epithelial layers as well as on endocrine-like cells. Such widespread distribution of this metabotropic GABA receptor is consistent with its significant modulatory role over intestinal motility, gastric emptying, gastric acid secretion, transient lower esophageal sphincter relaxation and visceral sensation of painful colonic stimuli. More intriguing findings, the mechanisms underlying which have yet to be determined, suggest GABAB receptors inhibit GI carcinogenesis and tumor growth. Therefore, the diversity of GI functions regulated by GABAB receptors makes it a potentially useful target in the treatment of several GI disorders. In light of the development of novel compounds such as peripherally acting GABAB receptor agonists, positive allosteric modulators of the GABAB receptor and GABA producing enteric bacteria, we review and summarize current knowledge on the function of GABAB receptors within the GI tract.

show abstract

“…resulted in a significant reduction of vagal efferent discharges evoked by baclofen, which was con firmed to be a sufficient dose to suppress the acid out put induced by baclofen (5,6). BPBA also prevented the vagal response to GABA.…”

mentioning

confidence: 85%

“…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).…”

mentioning

confidence: 99%

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

Yamasaki

Gotō

1992

Jpn.J.Pharmacol

Self Cite

View full text Add to dashboard Cite

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...

show abstract

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

Cited by 7 publications

References 29 publications

GABAB Receptor Signaling in the Dorsal Motor Nucleus of the Vagus Stimulates Gastric Motility via a Cholinergic Pathway

GABAB Receptor Signaling in the Dorsal Motor Nucleus of the Vagus Stimulates Gastric Motility via a Cholinergic Pathway

A Gut Feeling about GABA: Focus on GABAB Receptors

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

Contact Info

Product

Resources

About