Identification and Characterization of Muscarinic Receptors in Cultured Human Pancreatic Carcinoma Cells

Abstract

Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [³HIN-meth-ylscopolamine ([³HINMS). T³M⁴ and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [³HINMS also bound in PANC-I and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and 11-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyll-5, 11-dihydrodH-pyrido-[2, 3-b][1, 4] benzodiazepined-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 phospho-lipid hydrolysis.