Chemotaxis of human and rat leukocytes by the delta-selective non-peptidic opioid SNC 80.
Opioids like morphine, represent a major source of relief for most chronic moderate to severe nonmalignant pain. However, opioid abuse may lead to infections such as hepatitis and AIDS because opioids have been associated with suppressing various parameters of immune function including antimicrobial resistance, antibody production, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis. We have previously reported immunopotentiating properties of non-peptidic opioid receptor selective agonists and antagonists. In this study, we evaluated the effects of the nonpeptidic delta-opioid receptor agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC 80) on chemotaxis of rat thymic and human peripheral blood mononuclear cells by using a modified Wilkinson chamber. Cell recruitment is an essential process in acute and chronic inflammatory responses. We observed that SNC 80 at concentrations of 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) M, significantly (p < 0.01) stimulated rat thymic (1.3, 1.55, 1.58, 1.75, and 1.8-fold increases respectively) and human leukocyte (1.13, 1.37, 1.43, 1.7, 1.83 fold-increases respectively) chemotaxis (demonstrated by checkerboard assays), compared with untreated control. The effects of SNC 80 on chemotaxis of rat and human leukocytes were antagonized by naloxone, indicating that the modulation of chemotaxis by SNC 80 is via a classic opioid receptor. The development and use of non-peptidic opioids like SNC 80 could have an immediate impact not only as potent analgesics, but in immunoregulation.
Ordaz-Sánchez
Iván
I
Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, Mexico.
Weber
Richard J
RJ
Rice
Kenner C
KC
Zhang
Xiaoyan
X
Rodríguez-Padilla
C
C
Tamez-Guerra
R
R
Méndez-Vázquez
José L
JL
Gómez-Flores
R
R
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000166:cytology
D001549:Benzamides; D002630:Chemotactic Factors; D009292:Narcotic Antagonists; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009270:Naloxone