5532
Rania Abdullah Ali Salama
Investigation On The Effect Of Cannabinoid Agonists And Antagonists In Gastric Acid Secretion And Gastric Ulcer In Rats
Cannabinoid receptors. Carbachol . Gastric acid. Histamine Citation: Salama R A, Abdelsalam R M, Abdel‐Salam O M E, Khattab M M, Salem A S, El‐Khyat Z A, Morsy F A, Eldenshary ES (2018). Modulation of gastric acid secretion by cannabinoids in rats. J Biochem Mol Toxicol; e22256.
Cannabinoids are a family of complex chemicals that exert most of their actions through cannabinoid receptors (CBRs). Activation of CBRs is believed to exert a beneficial role in gastrointestinal discomfort, nausea, vomiting and secretion. G- protein- coupled receptors (GPCR); namely CB1R in enteric and central neurons and CB2R in immune system may have a role in regulation of acid secretion. Thus, the present study aimed to evaluate the role of CB receptors in regulation of gastric acid secretion and gastric mucosal damage in rats. To fulfill this aim the effect of cannabinoid CB1 and CB2 receptor agonists and antagonists on gastric acid secretion stimulated by histamine (5 mg/kg, s.c.), 2-deoxy-Dglucose (D-G) (200 mg/kg, i.v.) or carbachol (4 μg/kg, s.c.) in the 4h pylorus-ligated rat was investigated. Gastric wall mucin, gastric mucosal lesions and peptic activity were determined. Moreover, water immersion restrain ulcer (WIRS) model was used to study the effect of cannabinoids in induction of mucosal lesions. The present study revealed that NADA, 1 mg/kg, S.C. (CB1R agonist) inhibited gastric acid secretion stimulated by D-G and carbachol, reduced pepsin content and increase mucin secretion. Furthermore, it decreased both MDA and NO contents together with an increase in both GSH and PON-1. Meanwhile, AM630, 1 mg/kg, s.c. (CB2R antagonist) inhibited gastric acid secretion stimulated by DG, reduced MDA and NO contents along with an increase in GSH and PON-1. Furthermore, administration of NADA (CB1R agonist) and AM630 (CB2R antagonist) decreased the mucosal lesions, decrease the inflammatory neutrophil count, increased both GSH and PON-1 along with a decrease in MDA and NO contents and decreased inflammatory cytokines TNF- α, IL-1β and MPO contents in gastric mucosa. Therefore the CB1 agonist, NADA and CB2 antagonist, AM630 administrated to pylorus- ligated rats inhibited stimulated acid secretion, decreased gastric damage, reduced mucosal oxidative stress and have anti-inflammatory effect. These effects are likely to be mediated via activation CB1R receptor as well as TRPV1 receptor in stomach.
2019
Ph.d
Cairo
Pharmacy