ABSTRACT
The antisecretory effect of berberine sulfate (BS) was determined in the rabbit ileal mucosa in vitro mounted in Ussing chambers. When present in the luminal side, the drug had no effect on potential difference (PD) or on the short-circuit current (Isc) changes induced by theophylline or prostaglandin E2 (PGE2). When present in the serosal medium at a concentration of 2 mM, however, berberine reduced PD and Isc and abolished residual ion flux (bicarbonate secretion) but had no significant affect on basal net Na and Cl transepithelial transport. BS effect on basal PD was not affected by the absence of Ca2+ in the medium; neither was it inhibited by the alpha-adrenergic blocker yohimbine. Serosally added BS effectively antagonized the secretory effect on Isc of agents that increase each of the known intracellular mediators of ion secretion: cyclic 3',5'-adenosine monophosphate (cAMP), cyclic 3',5'-guanosine monophosphate (cGMP), and Ca2+; it also inhibited the ion transport modifications evoked by PGE2. The drug had no effect on the concentration of cyclic nucleotides either under basal condition or in the presence of some secretagogues. Finally, BS did not impair the PD rise due to luminal addition of glucose.
Subject(s)
Berberine Alkaloids/pharmacology , Berberine/pharmacology , Chlorides/pharmacokinetics , Ileum/metabolism , Sodium/pharmacokinetics , Animals , Basal Metabolism , Biological Transport/drug effects , Calcium-Binding Proteins/pharmacology , Cyclic GMP/analogs & derivatives , Cyclic GMP/pharmacology , Dinoprostone , Electrophysiology , Ileum/drug effects , In Vitro Techniques , Intestinal Mucosa/drug effects , Intestinal Mucosa/physiology , Ions , Male , Prostaglandins E/pharmacology , Rabbits , Theophylline/pharmacologyABSTRACT
The synthetic opiate loperamide (LPMD) is an antidiarrheal compound which affects both intestinal motility and the transport of water and electrolytes. We have investigated its effects on ion transport in the stripped ileal mucosa of rabbits, mounted in Ussing chambers in vitro. Addition of LPMD to serosal bathing medium resulted in a dose-dependent decrement of short-circuit current (Isc). LPMD (50 microM) significantly increased net Cl absorption (JClnet) and JRnet (assumed to represent HCO3 secretion). LPMD also inhibited the Isc increments evoked either by agents that increase 3',5'-cyclic adenosine monophosphate (cAMP) content (theophylline and prostaglandin E2) or by the Ca2+ ionophore A23187; the opiate, however, did not prevent the Isc change induced by 3',5'-cyclic guanosine monophosphate (cGMP)-related agents such as 8-Br-cGMP and Escherichia coli heat-stable enterotoxin. LPMD did not alter basal or secretagogue-stimulated tissue cAMP. In contrast, LPMD caused a small increase in cGMP content of stripped ileal mucosa, but not in that of isolated enterocytes. The role of Ca2+ in LPMD action is suggested by the significantly different effect of the drug on JClnet in the presence and in the absence of Ca2+ in the serosal solution.
