Identification and characterization of muscarinic receptors in cultured human pancreatic carcinoma cells

Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [³H]7V-meth-ylscopolamine ([³H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [³H]NMS also bound in PANC-I and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and ll-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5, ll-dihydro-6H-pyrido-[2, 3-b][l, 4] benzodiazepine-6-one (AF-DX 116) inhibited [3H]NMS binding and carbachol-mediated [3H]inositol monophosphate formation in both T3M4 and COLO-357 cells. The order of inhibition was: Atropine > PZ > AF-DX 116. Carbachol did not alter [3H]inositol monophosphate formation in the other cell lines. These findings suggest that the mAChRs expressed in some human pancreatic cancer cells exhibit the pharmacologic characteristics of a muscarinic receptor subtype with an intermediate affinity for PZ and a lower affinity for AF-DX 116 and are functionally coupled to activation of phospholipid hydrolysis.