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

• Published in: Pancreas Vol. 4; no. 3; p. 363
• Main Authors: Ackerman, M S, Roeske, W R, Heck, R J, Korc, M
• Format: Journal Article
• Language: English
• Published: United States 1989
• Subjects: Atropine - pharmacology; Carbachol - pharmacology; Cell Line; Humans; Inositol Phosphates - metabolism; Kinetics; N-Methylscopolamine; Pancreatic Neoplasms - metabolism; Parasympatholytics - metabolism; Pirenzepine - pharmacology; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Scopolamine Derivatives - metabolism; Tumor Cells, Cultured - metabolism
• ISSN: 0885-3177
• DOI: 10.1097/00006676-198906000-00014

Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]N-methylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANCI and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and 11-[[2-[(diethylamino) methyly]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-[2, 3-b] [1, 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 greater than PZ greater than 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.