Pentoxifylline does not act via adenosine receptors in the inhibition of the superoxide anion production of human polymorphonuclear leukocytes.
The inhibitory effect of adenosine (ADO) and pentoxifylline (POF) was studied alone and in combination on the N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated superoxide anion production of human polymorphonuclear leukocytes (PMNL). The pharmacological analysis of the results of these experiments demonstrated greater than additive and independent interaction of the drugs, representing potentiation. These results reflect differences between the sites of action of ADO and POF. Accordingly, the ADO receptor antagonist 8-phenyltheophylline only diminished the inhibition mediated by ADO, but totally failed to affect POF. Therefore, we hypothesize that POF acts as a phosphodiesterase inhibitor, potentiating the increase in cyclic AMP induced by ADO due to the stimulation of the adenylate-cyclase of human PMNL.
Thiel
M
M
Department of Anesthesiology, University of Munich, FRG.
Bardenheuer
H
H
Pöch
G
G
Madel
C
C
Peter
K
K
D000241:Adenosine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000378:metabolism*; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D004338:Drug Combinations; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D010431:Pentoxifylline