MDP and 5-HT receptors

A possible interaction of immunomodulator muramyl dipeptide (MDP) with 5-HT₇ (5-hydroxytryptamine) receptors was investigated. The activation of 5-HT₇ receptors relaxes the guinea-pig distal ileum. The whole ileum segments were, therefore, cut and placed into the bath. The preparations were precontracted by substance P and potently relaxed by adding incremental concentrations of 5-carboxamidotryptamine (5-CT) (0.01–3.2 μM), less potently by 5-hydroxytryptamine (5-HT) (1–100 μM). The preparations most sensitive to 5-CT were also relaxed by MDP (1–100 μM). Noncumulative concentration–response curves (CRCs) for 5-HT or 5-CT were established in the absence or presence of 5-HT antagonist metergoline (320 nM). Metergoline inhibited the relaxations and shifted the CRCs to the right. In the preparations most sensitive to the effects of both 5-CT and metergoline, the latter substance also inhibited the effect of the highest concentration (100 μM) in CRCs for MDP. In another type of experiments, CRCs for 5-HT or 5-CT were constructed in the presence of low concentrations of MDP (5–500 nM). The relaxations evoked by either drug remained unchanged. These results suggest that low concentrations of MDP do not interact with activation of 5-HT₇ receptors. In higher concentrations MDP acts on this receptor type as a very weak partial agonist.