Guanine nucleotides activate multiple signaling pathways in permeabilized gastric chief cells. Evidence for GTP gamma S-induced calcium-independent pepsinogen secretion
Nonhydrolyzable guanine nucleotide analogues were used to evaluate the role of guanine nucleotide binding (G) proteins in regulating pepsinogen secretion from streptolysin O-permeabilized chief cells from guinea pig stomach. In the presence of 100 nM calcium, 100 microM guanosine 5'-(beta,gamma...
Gespeichert in:
Veröffentlicht in: | The Journal of biological chemistry 1993-04, Vol.268 (12), p.8491-8496 |
---|---|
Hauptverfasser: | , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Nonhydrolyzable guanine nucleotide analogues were used to evaluate the role of guanine nucleotide binding (G) proteins in
regulating pepsinogen secretion from streptolysin O-permeabilized chief cells from guinea pig stomach. In the presence of
100 nM calcium, 100 microM guanosine 5'-(beta,gamma-imido)triphosphate or guanosine 5'-3-O-(thio)triphosphate (GTP gamma S)
caused a 2- to 4-fold increase in pepsinogen secretion. GTP gamma S stimulated secretion in the absence of calcium (up to
10 mM EGTA). With or without added calcium, GTP analogues caused a 2- to 3-fold increase in cAMP, whereas guanosine 5'-O-2-(thio)diphosphate
and calcium alone had no effect on cAMP levels. GTP analogue-induced activation of phospholipase C was evidenced by a calcium-independent
increase in cytidine diphospho-1,2-diacylglycerol levels (50% above basal). Phorbol ester- and GTP gamma S-stimulated phosphorylation
of a 72-kDa acidic protein was abolished by an inhibitor of protein kinase C (CGP 41251). However, GTP gamma S-induced pepsinogen
secretion was only partially inhibited by adding CGP 41251 or a protein kinase C inhibitor peptide. These results indicate
that guanine nucleotides activate major signaling pathways in gastric chief cells. Nevertheless, GTP gamma S can induce pepsinogen
secretion independently of changes in calcium, cAMP, or activation of protein kinase C. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)52901-X |