Calcium-sensing receptor: A new target for therapy of diarrhea

Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution(ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxinmediated excessive secretion, reduced absorption and compromised barrier function- the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calciumsensing receptor(Ca SR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears "all-inclusive": it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating Ca SR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of Ca SR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.

Effect of crude methanol leaf extract ofCombretum racemosum on histamine-stimulated gastric secretion in rats

Objective:To investigate the effect of crude methanolic extract of Combretum racemosum (C. racemosum) leaves on histamine-stimulated gastric secretion in rats. Methods: Phytochemical and acute toxicity tests were performed. Anti-secretory activity of C. racemosum extract was investigated in pyloric ligated rats administered histamine. Gastric juice was collected from all the animals and the volume, titratable acidity, pH and mucus content were measured. The effect of C. racemosum extract on calcium chloride induced contractions of the guinea-pig ileum suspended in high potassium, calcium-deficient depolarizing solution was investigated. The H2 receptor antagonistic potency was also evaluated using the isolated non-gravid rat uterus. Results:Phytochemistry revealed the presence of abundant amounts of saponins and moderate amounts of glycosides, terpenoids, proteins, reducing sugar, resins, alkaloids, flavonoids and carbohydrates. The oral LD50 of the extract was greater than 8000 mg/kg body weight in mice. Pretreatment of pyloric ligated rats with C. racemosum prior to histamine administration significantly reduced (P < 0.001) the volume of gastric juice and titratable acidity, and significantly increased (P < 0.001) gastric pH and gastric mucus when compared to the negative control. Both doses ofC. racemosum protected rats significantly (P < 0.001) from histamine-induced ulceration.C. racemosum potently inhibited contractions evoked by calcium chloride in a dose-dependent and reversible manner with an IC50 of 1132μg/mL.It also antagonized the relaxant effect of histamine on the isolated rat uterus in a manner comparable to cimetidine. Conclusions: The leaves of C. racemosum possess gastric anti-secretory and anti-ulcer effects and justify its use in traditional medicine in South-East Nigeria for the treatment of peptic ulcer disease.