A method for the bioassay of intestinal secretory activity in the conscious rat: studies with arachidonic acid and prostaglandin E2.

ABSTRACT

A method to study the kinetics of intestinal absorption and secretion in the unanesthetized rat is described. This procedure consists of the perfusion of the small intestine with isotonic NaCl-KCl-[36Cl]NaCl and polyethylene glycol-6000 as a nonabsorbable marker. Secretagogues [arachidonic acid (AA) or PGE2] were administered by continuous infusion via the superior mesenteric artery. Samples of perfusate, taken every 15 min, were analyzed for Na, Cl, 36Cl, K, and PEG-6000 to calculate solute and volume movement. In control rats, net absorption of water and electrolytes increased steadily throughout the 2-hr duration of the perfusion. Water, Na, and Cl moved across the intestine in parallel proportions. Net absorption of K was lower than that of the other electrolytes. AA, at the intraarterial dose of 1 mg/kg/hr did not produce a significant effect; at 4 mg/kg/hr it impaired net absorption, and at 8 mg/kg/hr it gradually enhanced net secretion of both water and electrolytes, especially K. Secretion was also demonstrated with the intraarterial infusion of PGE2 (312 microgram/kg). It is concluded that this new rat model is suitable for the bioassay of intestinal secretory stimulants and can be used for the search of intestinal antisecretory drugs.