Effect of cyclic AMP level reduction on human neutrophil responses to formylated peptides.
The increase in human neutrophil cyclic adenosine monophosphate (cAMP) levels evoked by formylated peptides is significantly reduced in the presence of MDL 12330A, SQ 22536, GDPssS and clonidine, which inhibit the adenylyl cyclase system by acting at different sites in this enzyme complex. A similar effect is exerted by adenosine deaminase and dipyridamole, which alter the extracellular adenosine concentration. Neutrophil preincubation with adenylyl cyclase inhibitors or dipyridamole reduces chemotaxis and superoxide anion production triggered by peptides; adenosine deaminase, on the contrary, has no effect on neutrophil responses. Our results seem to indicate that: (1) the peptide-induced increase in neutrophil cAMP is due mainly to an action on the adenylyl cyclase system; (2) an enhancement of this cyclic nucleotide, even slight and necessarily transient, is required for chemotaxis and O2 production induced in neutrophils by formylated peptides; and (3) cAMP does not represent the crucial second messenger for adenosine in the modulation of neutrophil responses.
Spisani
S
S
Dipartimento di Biochimica e Biologia Molecolare, Università Degli Studi di Ferrara, Italy.
Pareschi
M C
MC
Buzzi
M
M
Colamussi
M L
ML
Biondi
C
C
Traniello
S
S
Pagani Zecchini
G
G
Paglialunga Paradisi
M
M
Torrini
I
I
Ferretti
M E
ME
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D013481:Superoxides; C080504:formyl-methionyl-delta(Z)-dehydroleucyl-phenylalanine methyl ester; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004176:Dipyridamole; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D000241:Adenosine