Secretoneurin-induced in vitro chemotaxis of human monocytes is inhibited by pertussis toxin and an inhibitor of protein kinase C.
The sensory neuropeptide secretoneurin (SN) triggers chemotactic migration of monocytes. We have investigated the possibility that SN, like other chemoattractants such as formyl-Met-Leu-Phe and chemokines, might stimulate migration of monocytes by G protein and protein kinase C (PKC) activation and induce Ca2+i release. We report that preincubation of monocytes with pertussis toxin inhibited SN chemotaxis. Staurosporine, an inhibitor of PKC, significantly decreased SN-induced chemotaxis of monocytes, suggesting that PKC may be involved in the signaling. Tyrphostin-23, which inhibits tyrosin kinase, did not affect SN-induced chemotaxis of monocytes. This suggests that SN uses a signaling mechanism that is coupled to pertussis toxin-sensitive G proteins. Involvement of phospholipase C beta as a result of PKC activation is suggested by a SN-induced increase of intracellular Ca2+ concentration in monocytes.
Schratzberger
P
P
Department of Internal Medicine, Medical Faculty, University of Innsbruck, Austria.
Wöll
E
E
Reinisch
N
N
Kähler
C M
CM
Wiedermann
C J
CJ
D000814:Aniline Compounds; D002118:Calcium / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D053381:Secretogranin II; D020032:Tyrphostins; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014966:Xanthenes
D000814:Aniline Compounds; D002396:Catechols; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D009570:Nitriles; D053381:Secretogranin II; D020032:Tyrphostins; D010566:Virulence Factors, Bordetella; D014966:Xanthenes; C081159:secretoneurin; C059715:Fluo-3; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C060641:tyrphostin A23; D002118:Calcium