Pregnenolone Biosynthesis in the Rat Salivary Gland and Its Inhibitory Effect on Secretion

Miyashita, Takashi; Okubo, Migiwa; Shinomiya, Takashi; Nakagawa, Kan-Ichi; Kawaguchi, Mitsuru

doi:10.1254/jphs.10267fp

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…In a recent study using the present experimental system, pregnenolone, which is produced during the early stages of steroid biosynthesis, inhibited salivary secretion (29). In addition, pregnenolone enhanced the inhibitory effects of muscimol, which were blocked by bicuculline.…”

Section: Discussionsupporting

confidence: 43%

Rat Submandibular Gland Perfusion Method for Clarifying Inhibitory Regulation of GABAA Receptor

Okubo

Kawaguchi

2013

J Pharmacol Sci

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Abstract. GABA is an inhibitory transmitter found in rat salivary gland. However, the inhibitory potential of GABA on salivary secretion is unclear. Using an in vivo cannulation method, intraperitoneal administration of GABA was ineffective in the absence of gabaculine, a GABA transaminase inhibitor, on pilocarpine-induced salivary secretion, suggesting that GABA was rendered metabolically inactive before reaching the salivary gland. We hypothesized that the action of a drug on the salivary glands could be measured directly using a submandibular gland perfusion system. The submandibular gland artery, veins, and duct were cannulated in situ so that physiological functions such as innervation would not be compromised. Hank's balanced salt solution (pH 7.4) was perfused at a rate of 0.5 ml/min together with 1 M carbachol (CCh) over a 5-min period every 30 min. Amount of secreted saliva showed no change to the recurrent addition of CCh to the perfusate. GABA or muscimol dose-dependently inhibited CCh-induced salivary secretion. This effect was blocked by bicuculline, a GABA A -receptor (GABA A -R) antagonist, and enhanced by clonazepam, a central-type benzodiazepine-receptor agonist. These results suggest that salivary secretion is suppressed by GABA A -R in rat salivary gland and that the perfusion method used was effective in clarifying inhibitory regulation of GABA A -R.

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Section: Discussionsupporting

confidence: 43%

Rat Submandibular Gland Perfusion Method for Clarifying Inhibitory Regulation of GABAA Receptor

Okubo

Kawaguchi

2013

J Pharmacol Sci

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“…In an earlier study, our group showed that salivary secretion was also inhibited by a number of other drugs, diabetes, or psychological stress (Watanabe et al , ; Miyashita et al , ). It is therefore speculated that rebamipide may also reverse salivary dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Rebamipide, an anti‐ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines

et al. 2017

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“…enzyme (P450scc: CYP11A1), acts as an allosteric agonist of GABA A -R (30,31). From our recent study, it was speculated that steroid biosynthesis by CYP11A1 occurred in salivary gland and that salivary secretion induced by perfusion of rat MG with carbamylcholine chloride was inhibited by PRG (25). Expression of PRG enhances GABA A -R function, resulting in an increase in intracellular Cl − levels, followed by termination of Ca 2+ release from intracellular calcium stores and suppression of Cl − efflux throughout Ca…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, we have demonstrated that repetitive, but not single, administration of diazepam (DZP) at low doses (0.4 mg/kg) for more than 7 days markedly inhibited saliva secretion (in submission) and that perfusion of MG with PRG, a major neurosteroid produced by binding of DBI with its receptor, in rat suppressed carbacholinduced salivary secretion (25). Based on these observations, we hypothesized that DBI was involved in xerostomia in adult patients receiving long-term administration of clinical dosages of DZP or other benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

Diazepam Enhances Production of Diazepam-Binding Inhibitor (DBI), a Negative Saliva Secretion Regulator, Localized in Rat Salivary Gland

et al. 2011

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Abstract. Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, we investigated the effect of repetitive administration of diazepam (DZP) on salivary secretion and expression of DBI mRNA and peptide. Moreover, mRNA expression of PBR and pituitary adenylate cyclase-activating polypeptide (PACAP), a transcriptional regulator for DBI promoter, was evaluated after repetitive administration of DZP. Repetitive administration, but not single administration, of 0.4 mg/kg DZP caused inhibition of salivary secretion and enhanced expression of DBI, PACAP, and PBR mRNA in rat salivary gland, with an increase in production of DBI peptide. These results suggest that repetitive administration of DZP stimulates DBI production, which may result in an increase in the suppressive effect of DZP on salivary secretion.

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Pregnenolone Biosynthesis in the Rat Salivary Gland and Its Inhibitory Effect on Secretion

Cited by 7 publications

References 31 publications

Rat Submandibular Gland Perfusion Method for Clarifying Inhibitory Regulation of GABAA Receptor

Rat Submandibular Gland Perfusion Method for Clarifying Inhibitory Regulation of GABAA Receptor

Rebamipide, an anti‐ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines

Diazepam Enhances Production of Diazepam-Binding Inhibitor (DBI), a Negative Saliva Secretion Regulator, Localized in Rat Salivary Gland

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