Geranylgeranylacetone, a Novel Anti-Ulcer Drug, Stimulates Mucus Synthesis and Secretion in Rat Gastric Cultured Cells

Abstract

Aim of this study was to investigate the effect of geranylgeranylacetone (GGA) on mucus synthesis and secretion in rat gastric cultured cells, and their relationship to prostaglandin (PG) synthesis. Rate of mucus synthesis was estimated by incorporation of ³H-glucosamine into the cultured cells. Release of ³H-glucosamine from the cells, which were preincubated in the medium containing the radioactive isotope, into the culture media was measured for the evaluation of mucus secretion. PG production by the cultured cells was measured by radioimmunoassay. GGA increased glycoprotein synthesis in a dose-dependent manner (p < 0.01). Secretion of mucus from cultured cells was also significantly enhanced by GGA. GGA did not significantly increase PG (E₂ and I₂production. These results indicate that GGA has the ability to stimulate mucus production by the gastric epithelial cells, and this action may play an important role in protective effect of GGA. It is, however, unlikely that this effect of GGA is mediated by endogenous PGs.

Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat.

“…TPA is one of the drugs that have cytoprotective action against gastric injury induced by necrotizing agents (1-3). We reported previously that pretreatment with TPA can prevent gastric damage induced by absolute ET, and this action of TPA may be due to the stimulation of gastric mucus production (7,8). Arakawa et al demonstrated the protective effect of TPA against gastric injury caused by ET in human subjects (9).…”

“…As we previously reported. TPA has the ability to stimulate gastric mucus in a cell culture system (8). In addition, TPA acts as a scavenging agent of free radicals like hydroxyl radicals in gastric cultured cells (15).…”

Geranylgeranylacetone Protects Guinea Pig Gastric Mucosal Cells from Gastric Stressor-Induced Necrosis by Induction of Heat-Shock Proteins.

“…[17][18][19][20] we consider that the HSPs induced by GGA were responsible for its cytoprotective effect against the various gastric stressors (Fig. 3).…”

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

“…Irsogladine is also reported to protect the gastric mucosa by enhancing the mucosal integrity of the stomach through the facilitation of gap junctional intracellular communication and increasing the intracellular levels of 3Ј,5Ј-cAMP (Ueda et al, 1995;Kyoi et al, 2004). On the other hand, teprenone exhibits a protective effect in various models by stimulating the secretion of mucus and the expression of heat shock proteins (Terano et al, 1986;Suemasu et al, 2009). Although the precise mechanisms by which these drugs reduced the severity of the antral lesions in response to indomethacin plus paroxetine remain unknown, it is assumed that these mucosal protective drugs can be used as a prophylactic against gastric bleeding associated with SSRIs.…”