The muscarinic agonist pilocarpine inhibits DNA and interferon-gamma synthesis in peripheral blood mononuclear cells.
Lymphocyte basal DNA synthesis and proliferative responses to phytohemagglutinin (PHA) showed a dose-dependent (5 X 10(-5)-5 X 10(-3) M) inhibition by the muscarinic agonist pilocarpine, in contrast to the basal enhancing effect produced by the M2 muscarinic-nicotinic agonist carbachol. The effect of pilocarpine was reversed by both atropine (1 X 10(-6) M) and pirenzepine (1 X 10(-7)-1 X 10(-8) M), M1-M2 and M1 muscarinic antagonists, respectively. The effect of pilocarpine may thus be specific for the M1 muscarinic receptor. Pilocarpine also inhibited interferon-gamma (IFN-gamma)-PHA induced production, but was unable to reverse the pokeweed mitogen (PWM)-induced DNA synthesis. Distinct immunoregulatory activities are suggested for cholinergic muscarinic receptors M1 and M2.
Arzt
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ES
Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), República Argentina.
Fernández-Castelo
S
S
Diaz
A
A
Finkielman
S
S
Nahmod
V E
VE
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*
D010835:Phytohemagglutinins; D010862:Pilocarpine; D007371:Interferon-gamma; D004247:DNA