Mouse intraperitoneal potency

Despite the uncertainties in HOP for the toxins, there is reason to suspect that their mouse intraperitoneal potencies (MIP), the ri for the standard mouse bioassay system, do not bear a uniform relationship to them. Early pharmacological work ( ) on the paralytic shellfish toxins was conducted with shellfish extracts. 

Potency of Figure 2 a,b,and d in intraperitoneal mouse bioassay illustrates that the character of the chemical substituent at carbon 40 in part determines potency. Thus, T17 (GB-3 LD5q=0.17 mg/Kg body weight) is more potent than T34 (BTX-B,GB-2 LD5q=0,20 mg/Kg) and both are more potent than oxidized T34 (oxidized BTX-B LD5q=1.50 mg/ Kg. 

Intestinal inflammation may increase the expression of enteric opioid receptors (see below), and the potency of delta opioid agonists such as DPDPE ([D-Pen2,5]enkephalin) to decrease intestinal transit and mucosal permeability is enhanced in the inflamed mouse gut. The intraperitoneal administration of antisense oligodeoxynucleotides to knock down enteric delta opioid receptor expression is associated with decreases in the inhibitory effects of DPDPE on transit and permeability, particularly in the inflamed intestine [21]. 

However, both toxins have equal lethal potencies when injected parenterally (Arnon et al., 1984 Lyerly et al., 1985) about 50 ng of either toxin injected intraperitoneally is sufficient to kill a 25 g mouse (Lyerly etal., 1986). Furthermore, in the presence of sublethal amounts of ToxA, also ToxB is lethal when given by the intragastric route (Lyerly et al., 1985). Indeed both toxins seem to play a role in the disease, according to vaccination studies with toxoids (Libby et al., 1982). This is supported by a recent study on human colonic tissue (see section 12.5.1). 

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