Neurotensin, bradykinin and somatostatin inhibit cAMP production in neuroblastoma N1E115 cells via both pertussis toxin sensitive and insensitive mechanisms.
Neurotensin, bradykinin and somatostatin inhibited in a time- and concentration-dependent manner prostaglandin E1- or forskolin-stimulated cAMP production in neuroblastoma N1E115 cells. Cell treatment with 1 microgram/ml pertussis toxin for 6 hours reversed the inhibition elicited by peptides after short incubation periods (less than or equal to 1 min) but, in contrast, had no effect after longer incubation periods (greater than or equal to 3 min). Fluoroaluminate also inhibited prostaglandin E1-stimulated cAMP production in N1E115 cells, and this effect was not reversed by pertussis toxin. The 6 hour treatment with pertussis toxin was shown to be sufficient to ADP ribosylate virtually all of the 41 kD protein substrate corresponding to the alpha subunit of Gi. Protein kinase C activation with phorbol ester did not inhibit basal or stimulated cAMP production. Our data point to the existence of both pertussis toxin sensitive and insensitive mechanisms of neuropeptide-mediated inhibition of cAMP formation in N1E115 cells. The toxin insensitive response is not mediated by protein kinase C. The possibility is discussed that it results from the activation of a pertussis toxin insensitive G protein.
Bozou
J C
JC
Centre de Biochimie du CNRS, Université de Nice, France.
de Nadai
F
F
Vincent
J P
JP
Kitabgi
P
P
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D009447:Neuroblastoma; D009496:Neurotensin / Q000494:pharmacology*; D037342:Pertussis Toxin; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D009496:Neurotensin; D013004:Somatostatin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D001920:Bradykinin