Galanin inhibits gastrin release from isolated rat gastric G-cells.
Enzymatically isolated rat gastric mucosal cells (0.25% G-cells) were separated by counterflow elutriation, yielding a fraction in which the G-cell content was relatively enriched to 1.4%. In this fraction, basal gastrin release (mean +/- SE) was 31.1 +/- 1.3 pg.10(6) cells-1.60 min-1 and was stimulated by 10(-8) M neuromedin C (222.3 +/- 18.1% of basal), 10(-4) M carbachol (227.5 +/- 25.9%), 10(-6) M 12-O-tetradecanoylphorbol-13-acetate (TPA) (196.3 +/- 14.7%), and 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) (193.9 +/- 6.8%), respectively. The neuropeptide galanin was tested at 10(-10) to 10(-7) M. Galanin had no effect on basal gastrin release but reduced the responses to neuromedin C, carbachol, TPA, and DBcAMP. IC50 ranged between 1 X 10(-10) and 8.6 X 10(-10) M galanin. Although in the relatively enriched G-cell fraction D-cells were not detectable by immunocytochemistry, a low rate of somatostatin release was still measured by radio-immunoassay (5.3 +/- 0.5 pg.10(6) cells-1.60 min-1). However, galanin failed to increase this rate under basal conditions or in response to any of the stimulants tested. These results favor the assumption that galanin might exert a direct inhibitory effect on rat gastric G-cells. Galanin seems to interfere at an intracellular mechanism(s), which is induced by neuromedin C and carbachol and which is commonly activated by protein kinase C- and cAMP-mediated stimulation.
Department of Internal Medicine II, Technical University of Munich, Federal Republic of Germany.
W
W
Schepp
C
C
Prinz
C
C
Tatge
R
R
Håkanson
V
V
Schusdziarra
M
M
Classen
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001839:Bombesin / Q000494:pharmacology; D005260:Female; D019004:Galanin; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism
D005755:Gastrins; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D000632:Aminopyrine; D013004:Somatostatin; C040794:neuromedin C; D019004:Galanin; D001839:Bombesin