Bombesin-like peptides stimulate gastrin release from isolated rat G-cells.
Bombesin-like peptides as well as receptor-independent activators were tested for their effect on gastrin release from acutely dispersed rat gastric G-cells. The amphibian peptide bombesin as well as its mammalian analogues neuromedin B and neuromedin C stimulated gastrin release. Maximal responses were achieved with 10(-9) M bombesin (191.0 +/- 16.8% of basal release), 10(-8) M neuromedin C(205.9 +/- 17.6%) and 10(-7) M neuromedin B (162.2 +/- 10.4%), respectively. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and the synthetic diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) are receptor-independent activators of the protein kinase C. Both TPA (10(-6) M) and OAG (10(-5) M) stimulated gastrin release to 214.0 +/- 29.3% and 198.2 +/- 20.8% of basal, respectively. Calcium ionophore A23187 (10(-5) M) was the most effective stimulant tested (364.7 +/- 39.6%). Its effect was reversed by the calmodulin antagonist W 7 (10(-6)-10(-5) M). Finally, forskolin (10(-5) M), a direct activator of cAMP-formation, as well as the cAMP-analogue dbcAMP (10(-3) M) induced gastrin release. IN conclusion, neuromedin B is less potent and less effective than neuromedin C and bombesin in stimulating rat gastric G-cells. In addition, gastrin release is activated by calcium- and phospholipid-dependent as well as by cAMP-induced cellular signal transduction mechanisms.
Schepp
W
W
Department of Internal Medicine II, Technical University of Munich, F.R.G.
Prinz
C
C
Håkanson
R
R
Schusdziarra
V
V
Classen
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002498:Centrifugation; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005755:Gastrins; D010446:Peptide Fragments; D013449:Sulfonamides; D005576:Colforsin; C017967:W 7; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin