Smooth Muscle Stimulation by an Immunomodulatory Compound Muramyl Dipeptide: Does It Involve Serotoninergic System?

Kadlec, O.; Mašek, K.; Gulda, O; Růžička, Vladimír; Parant, M; Chedid, L

doi:10.1159/000137989

Cited by 20 publications

(2 citation statements)

References 4 publications

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“…A role for histamine or serotonin or both (either from uveal mast cells or platelets) in acute leakage response to glycopeptides is indicated by the fact that cyproheptidine was partially effective at inhibiting leakage for at least 7 h posttreatment. It is interesting to note that MDP has recently (31) and that cyproheptidine inhibits the binding of MDP and serotonin to macrophages (45).…”

Section: Discussionmentioning

confidence: 99%

Uveitis induction in the rabbit by muramyl dipeptides

Waters¹,

Terrell²,

Jones³

1986

Infect Immun

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Intraocular inflammation (uveitis) was produced in rabbits by intravenous or subcutaneous treatment with N-acetylmuramyl-L-alanyl-D-isoglutamine and several of its synthetic analogs at doses of -0.2 mg/kg in saline. A dose-dependent increase in permeability of the ocular blood-aqueous barrier as measured by leakage of protein or fluoresceinated dextran from the serum into the eye was observed from 2 to 14 h after glycopeptide treatment. Peak response occurred at approximately 3 h postdose. The lowest dose found to produce maximal vascular leakage for the most active glycopeptide analogs was 1 mg/kg. The adjuvant-inactive L-L stereoisomer of N-acetylmuramyl-L-alanyl-D-isoglutamine was inactive, even at doses as high as 10 mg/kg. Analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine which were homologous in the lactyl side chain were found to cause less uveitis. Chronic biweekly intravenous treatment of rabbits for 1 month with either N-acetyl-L-aaminobutyryl-D-isoglutamine or its lipophilic 6-O-stearoyl derivative at 1 mg/kg, but not with murabutide, resulted in leukocytic inflammatory lesions unique to the uveal tract of the eye. The uveitis was potentially reversible and occurred with decreased severity as long as 2 months after cessation of chronic treatment. Vascular leakage but not cellular infiltrate in the choroid could be modulated by pharmacologic means.

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Section: Discussionmentioning

confidence: 99%

Uveitis induction in the rabbit by muramyl dipeptides

Waters¹,

Terrell²,

Jones³

1986

Infect Immun

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“…Muramyl dipeptide does, indeed, bind to serotonin receptors [37,[48][49][50]. This insight resulted in a wide range of serotonin-like activities being discovered for muramyl peptides in addition to their sleep-like properties, including smooth muscle activation, fever induction, immunological enhancement, analgesia, and platelet activation [51][52][53][54][55][56]. Thus, a small peptide "model" for serotonin binding was useful in discovering and predicting serotonin receptor behavior for a most unexpected peptidoglycan.…”

Section: Peptide-monoamine Complexesmentioning

confidence: 99%

Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies

Root‐Bernstein¹,

Dillon²

2008

CPD

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Many examples of specific binding between small molecules are known that are associated with modified physiological and pharmacological activities. Conversely, the antagonism or synergism of small molecules is often correlated with specific binding between the molecules. It follows that small molecule binding can be used as a relatively quick, easy, and specific screen for functionally useful drug actions and interactions. These actions and interactions may manifest themselves as functional antagonisms; binding may correlate with enhancement or synergism; the formation of some complexes may yield clues about how drugs may be targeted to specific cell types in vivo and provide leads for the development of antidotes for drug overdoses or poisoning; the binding of one molecule to another may mimic receptor binding; and complexation may provide novel ways of protecting and delivering drugs. Relevant examples from each type of application are reviewed involving peptide-peptide interactions; peptide-aromatic compound interactions; aromatic-aromatic compound interactions; vitamin-aromatic compound interactions; and polycyclic compound interactions. We argue that screening for molecular complementarity of small molecules turns ligands such as neurotransmitters and their metabolites, hormones, and drugs themselves, into direct targets of drug development that can augment screening new compounds for activity against receptors and second messenger systems. We believe that the small molecule complementarity approach is novel, fruitful and under-utilized.

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Serotonin and Peptide Immunoneuromodulators: Recent Discoveries and New Ideas

Silverman

Karnovsky

1989

Advances in Enzymology - And Related Areas of Molecular Biology

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Smooth Muscle Stimulation by an Immunomodulatory Compound Muramyl Dipeptide: Does It Involve Serotoninergic System?

Cited by 20 publications

References 4 publications

Uveitis induction in the rabbit by muramyl dipeptides

Uveitis induction in the rabbit by muramyl dipeptides

Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies

Serotonin and Peptide Immunoneuromodulators: Recent Discoveries and New Ideas

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