MUSCARINIC-M(3) RECEPTOR-MEDIATED RELEASE OF GASTRIN FROM CANINE ANTRAL G-CELLS IN PRIMARY CULTURE

The functional role of the cholinergic nervous system in regulating gastrin release was investigated using enriched canine antral G cells. Gastrin content was 30.1 +/- 2.9 pmol per well and basal gastrin release was 900 +/- 27 fmol per well (n = 45). Carbachol (10(-8) to 10(-5) M) dose-dependently stimulated gastrin release with a maximal stimulatory response achieved at a concentration of 10(-5) M (330% over basal). To characterize the muscarinic receptor which mediates gastrin release from antral G cells, we examined the effect of three muscarinic receptor antagonists on carbachol-stimulated gastrin release; atropine (nonselective muscarinic receptor antagonist), pirenzepine (M(1) muscarinic receptor antagonist) and 4-DAMP (M(3) muscarinic receptor antagonist). Atropine (10(-9) to 10(-6) M), pirenzepine (10(-8) to 10(-5) M) and 4-DAMP (10(-9) to 10(-6) M) had no effect on the basal gastrin release. However, carbachol (10(-5) M)-stimulated gastrin release was effectively inhibited by atropine and 4-DAMP with K-i values of 0.48 and 0.66 nM, respectively. Pirenzepine at a high concentration (10(-5) M) also inhibited carbachol-stimulated gastrin release with a K-i value of 46.3 nM. These results suggest that the cholinergic nervous system directly stimulates gastrin release via M(3) muscarinic receptors located on antral G cells.