Dual modulation by adenosine of gastrin release from canine G-cells in primary culture.
The effects of adenosine on gastrin release were studied in enzymatically dispersed canine antral cells after 24-36 h in primary culture. We found two contrasting actions for adenosine: inhibition of forskolin-stimulated gastrin release and potentiation of bombesin-stimulated gastrin release. These actions appeared to be mediated by A1 and A2 receptors, respectively. Forskolin-stimulated gastrin release was reduced by adenosine and the A1-selective agonist N6-(L-2-phenylisopropyl)adenosine (L-PIA) but not by the A2-selective agonist 2-phenylaminoadenosine (CV 1808). This inhibition by adenosine was reversed by the preferential A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) as well as by the nonselective adenosine receptor antagonist 8-phenyltheophylline (8-PT). Incubation of the cells with pertussis toxin (200 ng, 8 h) reversed the inhibition by adenosine. In contrast, bombesin stimulation of gastrin release was potentiated by adenosine and CV 1808 but not altered by L-PIA. This effect was enhanced by DPCPX and was not altered by treatment of cells with pertussis toxin. In the absence of exogenous adenosine, 8-PT and DPCPX produced a small increase in basal and stimulated gastrin release. These data suggest dual modulation by adenosine of G-cell function. A1 receptors inhibit adenosine 3,5'-cyclic monophosphate (cAMP)-mediated gastrin release via a pertussis toxin-sensitive mechanism, whereas A2 receptors potentiated the response to cAMP-independent stimuli of gastrin release. Enhancement of gastrin release by adenosine antagonists suggests functional restraint by endogenous adenosine.
Schepp
W
W
Center for Ulcer Research and Education, Veterans Administration Wadsworth Hospital Center, Los Angeles, California.
Soll
A H
AH
Walsh
J H
JH
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D007700:Kinetics; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*
D005755:Gastrins; D011983:Receptors, Purinergic; D005576:Colforsin; D010660:Phenylisopropyladenosine; C026708:2-phenylaminoadenosine; D000241:Adenosine; D001839:Bombesin