Toxic mussels and okadaic acid induce rapid hypersecretion in the rat small intestine

The diarrheic activity of algal toxins in blue mussels (Mytilus edulis) has been quantitatively determined in ligated intestinal loops of the rat. Hepatopancreas from toxic mussels were disintegrated by freeze-pressing, and the homogenized tissue suspended in an equal amount (w/v) of buffer or in the liquid recovered after steaming. When such suspensions were injected into ligated loops of rat small intestine a rapid fluid secretion was observed. In contrast, the liquid from non-toxic mussel tissue homogenate was absorbed. Toxic tissue homogenates, liquid recovered after steaming of toxic mussels as well as purified okadaic acid produced maximum fluid accumulation in the loops within two hours. The maximum net fluid accumulation observed was ca 300 mg of weight increase per cm length of intestine. Within a range of 50-200 mg/cm the dose-response relationship was close to linear (r = 0.96, 0.99). In duplicate tests the average deviation from the mean was +/- 9 mg/cm (SD = +/- 4.9). Mussels yielding less than 100 mg/cm of weight increase per g hepatopancreas have been allowed for human consumption, a quantity agreeing with the allowed level of okadaic acid. The minimum quantity of okadaic acid which produced significant secretion in the rat intestinal ligated loop test was approx. 0.5 microgram. On a body weight basis, therefore, humans are estimated to be at least four times as sensitive as the rat to enteral challenge with okadaic acid.