MDP and 5-HT receptors. Does MDP interact with 5-HT(7) receptors?
A possible interaction of immunomodulator muramyl dipeptide (MDP) with 5-HT(7) (5-hydroxytryptamine) receptors was investigated. The activation of 5-HT(7) 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 microM), less potently by 5-hydroxytryptamine (5-HT) (1-100 microM). The preparations most sensitive to 5-CT were also relaxed by MDP (1-100 microM). 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 microM) 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-HT(7) receptors. In higher concentrations MDP acts on this receptor type as a very weak partial agonist.
Sevcík
J
J
Institute of Pharmacology, Academy of Sciences of the Czech Republic, Videnská 1083, 142 20 4, Prague, Czech Republic. sevcik@biomed.cas.cz
Rûzicka
V
V
Slánský
J
J
Masek
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D008711:Metergoline; D012701:Serotonin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047087:5-carboxamidotryptamine