Characterization of muscarinic acetylcholine receptors in the isolated gastric chief cells from guinea pig

The muscarinic receptor system involved in pepsinogen secretion from isolated guinea pig gastric chief cells was investigated by assessing the effect of muscarinic receptor antagonists on carbamylcholine (CCh)-induced pepsinogen secretion. CCh stimulated pepsinogen secretion in a dose dependent manner with the maximal and the half-maximal stimulatory concentrations at 10(-4) and 3 x 10(-6) M, respectively. Each of five different muscarinic receptor antagonists such as atropine, pirenzepine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), AF-DX116 and scopolamine reduced pepsinogen secretion stimulated by graded concentration of CCh, but did not alter the maximum secretion. The increase in concentration of each antagonist caused parallel rightward shift of the dose response curve to CCh. Schild analysis of the inhibition of CCh-induced pepsinogen secretion by the antagonists showed that pA2 values of atropine, scopolamine and 4-DAMP are 8.8, 9.2 and 9.0, respectively. On the other hand, pA2 values of pirenzepine and AF-DX116 are 6.5 and 5.9, respectively, suggesting that the muscarinic receptor mediating pepsinogen secretion from chief cells has a intermediate affinity for pirenzepine and a low affinity for AF-DX116. These results suggest that the muscarinic acetylcholine receptor mediating pepsinogen secretion from gastric chief cells is the M3 subtype.